Chemical Structural Formula Research Articles

Omega-3 polyunsaturated fatty acids play a protective role in a mouse model of Parkinson's disease by increasing intestinal inducible Treg cells.

Parkinson's disease (PD) is defined as a progressive neurodegenerative disease in middle-aged and elderly people. The therapeutic effect of ω-3 PUFAs in several neurodegenerative diseases has been well recognized. Nevertheless, whether nutrition supplementing ω-3 PUFAs exerts a neuroprotective role in PD remains elusive. Bioinformatics revealed 2D chemical structural formula of three components. Mice received indicated treatment with saline, MPTP or ω-3 PUFAs according to grouping. Behavioral function of mice was measured through motor tests such as rearing, akinesia, and rotarod tests. OFT test measured anxiety-like behaviors of mice. Western blotting and TUNEL staining measured dopaminergic fibers and neurons of mice. Western blotting measured inflammation and apoptosis-related protein levels in mouse tissue. FACS measured iTreg cell proportion in colon and brain tissues of mice. ω-3 PUFAs repaired MPTP-stimulated motor function damage in PD mice. ω-3 PUFAs mitigated MPTP-stimulated comorbid anxiety in PD mice. ω-3 PUFAs relieved MPTP-stimulated deficits of dopaminergic fibers and neurons in PD mice. ω-3 PUFAs repressed MPTP-stimulated inflammation and apoptosis pathway activation in PD mice. ω-3 PUFAs repaired MPTP-stimulated immune function damage in PD mice. ω-3 PUFAs exert a protective role in PD mice through alleviating motor function impairment and neuroinflammation by increasing intestinal inducible Treg cells, which may provide a new direction for seeking targeted therapy plans for PD in humans.

Study on the Simplified Chemical Kinetic Combustion Mechanism of Mixed Methanol/PODE Fuel for Marine Diesel Engines

As a clean alternative fuel oil for marine engines, methanol has received increasing attention, but its low cetane number requires diesel ignition, which increases the difficulty of retrofitting existing engine fuel injection systems. Polymethoxy dimethyl ether (PODEn) is an ether fuel mixture whose chemical structural formula can be expressed as CH3O(CH2O)nCH3 (n≥2). PODE3 is the predominant component in the blend, and its properties are representative of the blend. PODE is a low-carbon fuel with a high cetane number and is easy to compression ignite, and, as such, can be used to ignite methanol in a marine diesel engine. This article explores the combustion mechanism of mixed methanol–PODE fuel using the characteristics of PODE that can be easily mixed with methanol for combustion. Taking methanol and PODE3 as representative fuels, the detailed combustion mechanism of PODE3 and the detailed combustion mechanism of methanol are simplified using a DRGEPSA (direct relationship graph with error propagation (DRGEP) and sensitivity analysis (SA)) method. Based on the target engine cylinder combustion environment, a simplified mechanism for mixed methanol–PODE fuel is obtained, and the new mechanism is validated in terms of the ignition delay period and laminar flame speed. The results indicate that the newly constructed simplified mechanism is basically consistent with the ignition delay data and flame propagation speed data measured by a rapid compression machine (RCM), laying the foundation for the application of alternative methanol fuels in marine engines.

Self-similar hierarchical honeycombs in two different fractal layouts: A comparative study of the in-plane crushing behaviors

This paper provides a new avenue for the development of cellular structures. By mimicking the chemical structural formula of the TpPB-Fe coordination polymer, a new self-similar hierarchical honeycomb was proposed. With respect to the existing self-similar hierarchical honeycomb in the literature which was constructed by replacing every three-edge vertex of the regular hexagonal honeycomb with a smaller hexagon, the new one is created by setting the fractal position at the midpoint of the cell walls of the regular hexagonal honeycomb. What I am really curious about is the difference in mechanical properties between the two self-similar hierarchical honeycombs. Finite element (FE) model was first built and validated by comparing against the existing theoretical data. Subsequently, the in-plane crushing behaviors of the honeycombs under different impact velocities were fully investigated by FE simulations. The deformation modes, plateau stress as well as the energy absorption capability of the honeycombs were studied. Different macroscopic and microscopic deformation patterns between the two hierarchical honeycombs were observed. The plateau stress of the new hierarchical honeycomb is higher than that of both the existing counterpart and the basic regular hexagonal one. Under low- and medium-velocity impact loading, the new honeycomb with low fractal ratio (α) has superior energy absorption capability with respect to the existing counterpart and the basic regular hexagonal one. However, the new honeycomb will lose its advantage in energy absorption when the fractal ratio or the impact velocity is large.

Ammonium-Bearing Fluorapophyllite-(K) in the Magnesian Skarns from Aleului Valley, Pietroasa, Romania

An ammonium-bearing fluorapophyllite-(K) occurs as a late hydrothermal product in the outer endoskarn zone from Aleului Valley (N 46°37′04″, E 22°35′22″), located at the contact of the granodiorite laccolith from Pietroasa, of Upper Cretaceous age, with Anisian dolostones. Associated minerals are wollastonite, K feldspar, diopside, fluorapatite, talc, and pectolite. The chemical structural formula is [K0.985Na0.012(NH4)0.076]Σ=1.073(Ca4.009Mn0.001Fe2+0.003Mg0.002Ba0.001)Σ=4.016(Si7.953Al0.047) O20.029[F0.899(OH)0.101]·8.059H2O. The structure was successfully refined as tetragonal, space group P4/mnc, with cell parameters of a = 8.9685(1) Å and c = 15.7885(5) Å. The indices of refraction are ω = 1.534(1) and ε = 1.536(1). The calculated density is Dx = 2.381 g/cm3, in good agreement with the measured density, Dm = 2.379(4) g/cm3. The thermal analysis shows that the mineral completely dehydrates at up to 450 °C (endothermic effects at 330, 371, and 448 °C) and loses ammonium at 634 °C. In the infrared spectra, the multiplicity of the bands assumed to be silicate modes (1ν1 + 3ν3 + 2ν2 + 3ν4) agrees with the reduction in the symmetry of the SiO44− ion from Td to Cδ. Fluorapophyllite-(K) from Aleului Valley is of late hydrothermal origin and crystallized from F-rich fluids originating from the granodiorite intrusion, which mobilized K, Ca, and Si from the pre-existing feldspar.

Bioinformatics analysis of rheumatoid arthritis tissues identifies genes and potential drugs that are expressed specifically

Studies have implicated necroptosis mechanisms in orthopaedic-related diseases, since necroptosis is a unique regulatory cell death pattern. However, the role of Necroptosis-related genes in rheumatoid arthritis (RA) has not been well described. We downloaded RA-related data information and Necroptosis-related genes from the Gene Expression Omnibus (GEO), Kyoto Gene and Genome Encyclopedia (KEGG) database, and Genome Enrichment Analysis (GSEA), respectively. We identified 113 genes associated with RA-related necroptosis, which was closely associated with the cytokine-mediated signaling pathway, necroptosis and programmed necrosis. Subsequently, FAS, MAPK8 and TNFSF10 were identified as key genes among 48 Necroptosis-associated differential genes by three machine learning algorithms (LASSO, RF and SVM-RFE), and the key genes had good diagnostic power in distinguishing RA patients from healthy controls. According to functional enrichment analysis, these genes may regulate multiple pathways, such as B-cell receptor signaling, T-cell receptor signaling pathways, chemokine signaling pathways and cytokine-cytokine receptor interactions, and play corresponding roles in RA. Furthermore, we predicted 48 targeted drugs against key genes and 31 chemical structural formulae based on targeted drug prediction. Moreover, key genes were associated with complex regulatory relationships in the ceRNA network. According to CIBERSORT analysis, FAS, MAPK8 and TNFSF10 may be associated with changes in the immune microenvironment of RA patients. Our study developed a diagnostic validity and provided insight to the mechanisms of RA. Further studies will be required to test its diagnostic value for RA before it can be implemented in clinical practice.

Carbonate-Bearing, F-Overcompensated Fluorapatite in Magnesian Exoskarns from Valea Rea, Budureasa, Romania

A carbonate-bearing, fluorine-overcompensated fluorapatite (F = 4.42 wt.% as compared with 3.77 wt.% F in the Ca5(PO4)3F end-member), was identified in forsterite-bearing skarns from Valea Rea (N 46°39′48″, E 22°36′43″), located near the contact of the granodiorite laccolith from Budureasa, of Upper Cretaceous Age, with Anisian dolostones. The chemical structural formula (with carbonate not included) is: (Ca4.989Mn0.001Fe2+0.003Mg0.003Ce0.001La0.001)(P2.992Si0.008)(O11.894F1.202Cl0.001). No major structural distortions due to (CO3F)3--for-(PO4)3- replacement were identified by single crystal X-ray diffraction, Raman or FTIR. The mineral crystallizes in space group P63/m, having as cell parameters a = 9.3818(1) Å and c = 6.8872(1) Å. The indices of refraction are: ω = 1.634(2) and ε = 1.631(1). The calculated density is Dx = 3.199 g/cm3 and the measured density is Dm = 3.201(3) g/cm3. Calculation of the Gladstone–Dale compatibility indices gave in all cases values indicative of superior agreement between physical and chemical data. In the infrared spectra, the multiplicity of the bands assumed to phosphate modes (1ν1 + 2ν2 + 3ν3 + 3ν4) agrees with the reduction of the symmetry of PO43− ion from Td to C6. Chemical peculiarities and textural relations agree with a hydrothermal origin of the mineral, crystallized from F-rich fluids originating from the granodiorite intrusion.

Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports

Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports

Computing Gutman Connection Index of Thorn Graphs

Chemical structural formula can be represented by chemical graphs in which atoms are considered as vertices and bonds between them are considered as edges. A topological index is a real value that is numerically obtained from a chemical graph to predict its various physical and chemical properties. Thorn graphs are obtained by attaching pendant vertices to the different vertices of a graph under certain conditions. In this paper, a numerical relation between the Gutman connection (GC) index of a graph and its thorn graph is established. Moreover, the obtained result is also illustrated by computing the GC index for the particular families of the thorn graphs such as thorn paths, thorn rods, thorn stars, and thorn rings.

Co(II) and Ni(II) bis(salamo)-based tetraoxime complexes: Syntheses, structural characterizations, fluorescence properties, and Hirshfeld analyses

Two new asymmetric complexes with the chemical structural formulas [{Co2(L)(μ 2-OH)}{Co2(L)(OAc)(CH3OH)}{Co2(L)(μ 2-OCH3)}{Co2(L)(μ 2-OAc)}]⋅4CH3OH and [Ni2(L)(μ 2-OAc)(CH3OH)]⋅CH2Cl2⋅3CH3OH have been synthesized from cobalt(II) acetate, nickel(II) acetate, and a bis(salamo)-based tetraoxime ligand derived from 3-bromo-5-chlorosalicylicaldehyde and 4-tert-butyl-2,6-diformylphenol, respectively, and characterized by elemental analyses, IR, UV–vis, fluorescence spectra, and single-crystal X-ray diffraction analyses. The Co(II) complex unit cell contained four crystallographically independent and chemically different heterotrinuclear complexes (molecules A, B, C, and D). The crystal structure included eight Co(II) ions, four completely deprotonated ligand (L)3− moieties, one bridging hydroxide, one monodentate acetate, one bridging methoxy, one bidentate chelating acetate, one coordinated methanol, and four crystallization methanol molecules. The Ni(II) complex had a dinuclear structure. The crystal structure of the Ni(II) complex included two Ni(II) ions, one completely deprotonated ligand (L)3−, one bidentate bridging acetate, one coordinated methanol, one crystallized dichloromethane, and three crystallized methanol molecules. Hirshfeld surface analyses showed that the complexes are stable. Furthermore, the fluorescence quenching of the Co(II) and Ni(II) complexes with H3L further confirmed the above experimental results.

Thermal rearrangements during liquid–vapor phase pyrolysis polycondensation of polysilane to high-functional polycarbosilane: spectral and thermal studies

Thermally induced Kumada rearrangement of –Si–Si– linear chains in polysilanes to –Si–C– chain was conducted in the liquid–vapor phase, followed by isothermal treatments at 410, 460 °C and pressure of 15 kgf cm−2 leading to polycarbosilane(PCS) with higher silane (–Si–H) content in the range 0.46–0.58 mass%. Molecular and thermal changes during the oligomer to polymer transformation were investigated, applying spectral and thermal techniques. FTIR, Raman, and 1H, 13C, and 29Si-NMR analytical results established the chemical structural formula, –Si–Si–, –Si–C–, –Si–H bonding networks, and evolution of –Si–H functionality in as-synthesized polycarbosilane during the thermal transformations. FTIR and 29Si-NMR studies followed the increase in silane content (–Si–H). Raman data revealed the formation and disappearance of –Si–Si– functional group as the transformation progresses. Average molecular mass increased proportionally with polymerization reaction time. Thermogravimetric studies at 1400 °C confirmed a polymer to ceramic conversion (ceramic yield) of as-synthesized PCS increased with the increase in mass average molecular mass and found to be as high as 88% mass. The formation of a high purity green β-SiC powder on heat treatment at 1500 °C confirmed the high molecular polycarbosilane.

Finding a Maximum Common Subgraph from Molecular Structural Formulas through the Maximum Clique Approach Combined with the Ising Model.

We examined the maximum common subgraph (MCS) of four neuraminidase inhibitors that were antiviral medication for treating and preventing type A and B influenza viruses. The MCS was obtained by finding a maximum clique of an association graph constructed from the two input chemical structural formulas. Maximum clique problem was reformulated to Ising Hamiltonian to allow for applying various techniques for optimization. We observed that the combined label for a vertex composed of elemental species and chemical bonds significantly worked well for decreasing the number of vertices in the association graph, which in turn helped to reduce the computational cost.

Tyrosine 135 of the β1 subunit as binding site of BAY-543: Importance of the Y-x-S-x-R motif for binding and activation by sGC activator drugs

Soluble guanylyl cyclase (sGC), the major receptor for nitric oxide (NO), is a heterodimer consisting of two subunits, the α and the β subunit. The NO/sGC/cGMP signaling pathway is protective in different disease pathomechanisms including angina pectoris, pulmonary hypertension and fibrotic diseases. The natural ligand heme has two carboxylic acids which interact in the β1 heme nitric oxide oxygen binding (HNOX) domain with the amino acids of the highly conserved Y-x-S-x-R motif. The Y-x-S-x-R motif is also involved in binding of the dicarboxylic activators cinaciguat and BAY 60–2770 as indicated by crystallization studies of sGC activator and bacterial HNOX homologs. To what extent the Y-x-S-x-R motif hydrogen bond network contributes to binding of monocarboxylic acids has not been examined so far. In the current paper, the chemical structural formula of the novel monocarboxylic drug BAY-543 is described for the first time. Using this novel drug, we evaluate the importance of the amino acids Y135 and R139 for thermostabilization and activation in comparison to the dicarboxylic acid BAY 60–2770. Measurements with point mutated sGC variants demonstrate tyrosine 135 as exclusive binding site of the monocarboxylic acid BAY-543 but not the dicarboxylic BAY 60–2770.

A Retrieval System of Medicine Molecules Based on Graph Similarity

Medicine information retrieval has grown significantly and is based on the structural similarity of medicine molecules. The chemical structural formula (CSF) is a primary search target as a unique identifier for each compound in the research field of medical information. This paper introduces a graph-based CSF retrieval system, PharmKi, which accepts the photos taken from smartphones and the sketches drawn on the tablet PCs as inputs. To establish a compact yet efficient hypergraph representation for molecules, we propose a graph-isomorphism-based algorithm for evaluating the spatial similarity between graphical CSFs. An indexing strategy based on the graph TF-IDF technology is also introduced to achieve a high efficiency for large-scale molecule retrieval. The results of comparative study demonstrate that the proposed method outperforms the existing methods on accuracy, and performs well on efficiency.

Precise Construction and Tuning of an Aerolysin Single-Biomolecule Interface for Single-Molecule Sensing

Precise Construction and Tuning of an Aerolysin Single-Biomolecule Interface for Single-Molecule Sensing

Academic Detailing from the Viewpoint of Chemical Structural Formulas

In order to implement academic detailing, it is extremely important to understand the pharmacological activity of drugs based on their chemical structures. To construct a database for academic detailing, a viewpoint for clinically utilizing the fundamental pharmacological features of a drug is required. These fundamental pharmacological features include chemical characteristics such as chemical structures, physical characteristics such as pharmaceutical formulations for efficient drug delivery to target organs, and a pharmacological viewpoint, which is a mechanism by which a drug is determined to be effective. In addition, in vivo kinetics are included in a drug's pharmacological features, i.e., a drug's excretion through urine and feces via the kidneys, its side effects due to differences in enzyme type when the drug is metabolized in the liver, as well as the capacity of the patient's current enzyme profile. This review describes academic detailing based on the chemical structure of drugs for breast cancer hormone therapy, as an example.

Questionnaire Survey to Pharmacists after a Workshop on the Chemical Structural Formula of Drugs

Recently, it has been reported that only a small number of sixth-year students who had undergone a long-term pre-clinical training in the fifth year found organic chemistry useful. To explain this, we hypothesized that pharmacists are unable to utilize the knowledge of organic chemistry to solve clinical problems. With the aim of addressing this problem, we conducted a workshop consisting of a series of lectures and exercises on structural similarity, solubility, absorption, and metabolism of drugs based on a chemical structural formula. Then, we administered a questionnaire survey to 253 participants who had participated in our workshop. The questionnaire comprised 17 questions, and free descriptions were analyzed using text mining. Results showed that, although about 45% of the participants confirmed the chemical structural formula described in the medical package insert, and about 22% of the participants had the opportunity to check the metabolites described in the drug interview form, more than 90% of the participants were interested in the workshop contents. Thus, pharmacists may want to learn how the process of utilizing the chemical structural formula can be applied to their clinical practice.

Influence of heating procedures on the surface structure of stabilized polyacrylonitrile fibers

Abstract The stabilized polyacrylonitrile (PAN) fibers were obtained after heating the precursor PAN fibers under air atmosphere by different procedures. The surface structures and compositions of as-prepared stabilized PAN fibers have been investigated by SEM, SSNMR, XPS and Raman spectroscopy. The results show that 200 °C, 220 °C, 250 °C, and 280 °C are key temperatures for the preparation of stabilized PAN fibers. The effect of heating gradient on the structure of stabilized PAN fibers has been studied. The possible chemical structural formulas for the PAN fibers is provided, which include the stable and unstable structure. The stable structure (α-type) could endure the strong chemical reactions and the unstable structure ( β - or γ -type) could mitigate the drastic oxidation reactions. The inferences of chemical formula of stabilized PAN fibers are benefit to the design of appropriate surface structure for the production for high quality carbon fibers.

長期放置された農薬瓶に発生した硫化水素の1例(A case of hydrogen sulfide generated in agricultural chemical bottles left unused for a long time)

症例は80歳男性。自宅台所で内容不明の褐色の小瓶5本を見つけ，廃棄のため開栓したところ刺激臭のあるガスが噴出し失神した。家族が駆けつけると痙攣しており救急要請した。10分後救急隊現着時，傷病者の意識は回復しており自力歩行可能であった。傷病者からは硫黄臭がした。室内に硫黄臭はなかったが硫化水素中毒を疑い傷病者を搬送。病院着後脱衣，除染を行い救急外来に搬入した。傷病者は意識清明であり，事故当初のことも覚えていた。硫化水素中毒に準じ肺水腫等の発生を考え経過観察入院とした。第2病日の胸部レントゲン写真，血液検査等でも問題なく，第3病日に軽快退院となった。小瓶の分析を科学捜査研究所が行った。5瓶ともに内容は古い農薬であり，瓶のラベルは変色していたが内容物のサプロール（殺菌剤），スリトーン（成長抑制剤）等が判読できた。発生したガスを分析したところ硫化水素とイミダゾリジンチオンが検出された。カーバメート系殺虫剤が長期放置され経年変化によりイミダゾリジンチオンに分解，酸化され，硫黄基を含むこれがさらに分解され，硫化水素が発生したと考えられた。長期に農薬を放置すると，保管の状況によっては硫化水素等の中毒物質が発生することもあり，市民には長期保管しないことを喚起することが必要である。また救急の現場においては中毒物質による意識障害にも注意して傷病者への接触を図ることが2次災害防止の観点からも重要である。 An 80–year–old man found five small brown bottles with unknown contents in his house. When he opened the bottles for the sake of disposal, gas with an irritating odor spouted from the bottles, and he fainted away. His family called an ambulance because he was cramping. When an emergency ambulance crew arrived, the patient was already conscious and was able to walk. He smelled sulfurous. Under suspicion of hydrogen sulfide poisoning, the patient was admitted to our hospital to observe for possible occurrence of pulmonary edema or other abnormalities. Chest radiography, blood examination, and other tests performed on the second hospital day revealed no abnormalities, and the patient was discharged in good condition on the third hospital day. The small bottles were submitted to a forensic science laboratory for analysis. The bottle contained old agricultural chemicals. Analysis of the generated gas detected hydrogen sulfide and imidazolidinethione. It was presumed that the carbamate drug left in the bottles for a long period was decomposed into imidazolidinethione and was oxidized under secular change, and the produced imidazolidinethione having a sulfur group was further decomposed to generate hydrogen sulfide. 意識消失，痙攣発作等で救急要請されることは日常的であるが，その原因が薬物中毒であることもあり，鑑別診断が必要となる。今回我々は経年変化を来した農薬瓶から硫化水素が発生し，意識消失，痙攣発作を来した症例を経験した。農薬等も保管の状況によっては偶発的に中毒物質が発生することもあり，市民には農薬等を長期放置しないよう注意喚起が必要である。また救急の現場においても，2次災害防止の観点からも重要であり，興味ある症例と考えられたため報告する。 患 者：80歳の男性 主 訴：意識消失，痙攣 既往歴：高血圧症，前立腺肥大症があり内服加療中 現病歴：6月某日，本人の呻き声が聞こえたため2階から降りてきた娘が，台所で痙攣し意識消失している傷病者を発見し，救急要請を行った。傷病者の意識レベルは事故から3分程度で改善した。要請10分後に救急隊が到着した時には傷病者は自力で着替えができるほど回復していた。救急隊接触時，傷病者からは硫黄臭がした。傷病者は自力歩行で救急車に乗車した。当該救急隊より当院へ収容の依頼があり，硫化水素中毒を疑うとの報告を受け，その対応，準備を行った。当直医は病院着後，傷病者を脱衣し水除染を行った後，救急外来に収容した。 入室時現症：意識清明，GCS E4V5M6。会話可能な状態であり，意識消失した時のことも覚えていた。軽度の眼痛，頭痛を訴えるも，嘔気などなく，振戦，複視，チアノーゼ等は認めなかった。 来院時現症：BP 164/74mmHg，HR 59/分，SpO2 100%（酸素10L/分）。四肢麻痺なし。瞳孔不同なし，対光反射は正常，心音，呼吸音は清であった。モニター心電図上不整脈を認めなかった。除染後もまだ頭髪等より硫黄臭がした。 検査所見：来院時の血液検査所見をTable 1に示す。血液ガス所見は，酸素マスク10L/分投与でPO2 298mmHg，COHb 0.6%でありとくに異常を認めなかった。 入室後経過：傷病者より受傷時の状況を聴取した。妻に頼まれ台所にあった内容不明の褐色の小瓶5本を処分しようと開栓したところ刺激臭のあるガスが噴出し，失神したとのことであった。硫黄臭，意識消失，痙攣などの所見からも硫化水素中毒を疑い，これに準じた治療を行うこととし，肺水腫等の発生を考え経過観察入院とした。第2病日の胸部レントゲン写真，血液検査等でも問題なく，とくに訴えもなかったため第3病日に軽快退院となった。受傷時台所の近くにいた妻は無事であった。 事故発生時の当該救急隊は，硫黄臭から硫化水素中毒を疑い，救急搬送を決めた時点で毒ガス漏洩の可能性を考え通信指令室に消防隊の応援を要請し，司令室からは警察に連絡し消防とともに傷病者宅の調査を行った。当該の小瓶は傷病者宅の玄関先にビニール袋に入れて家族が放置していたが，かすかに硫黄臭がした。家族が容器の内容物を台所の流し台に捨てたため，台所周辺には硫黄臭がしていた。応援消防が傷病者宅周辺の異臭の調査を行ったが，異臭の拡大は認めなかった。当該消防は中毒を疑う薬物の調査のため応援消防隊に空ビンの回収を指示した。瓶は茶褐色で内容量は100mLであり，ラベルは古く茶褐色に変色し，商品名は判読できなかった。農薬と考えられたが主成分は不明であり，ラベルの成分表記の部分はサプロール（殺菌剤），スリトーン（成長抑制剤）等が何とか判読できた。担当警察は小瓶内容の分析のために警察本部科学捜査研究所で分析を行った。後日，当院より傷病者の健康被害を考え，科学捜査研究所に検出された薬物に関しての情報提供を依頼した。しかし分析結果の詳細な返答はなく，5本あった瓶の内容は同じで，噴出したものが気体であり，これを分析したところ硫化水素とイミダゾリジンチオンが検出されたとのことであった。小瓶内の液体の分析結果に関して回答はなかったが，内容物が変性し硫化水素が発生したことから，もとの内容物はカーバメート系殺虫剤が含まれているであろうとの回答を得た。 今回の農薬の瓶は未開封であり，もともと硫化水素が含まれていたとは考えられず，また事故の発生状況からも何らかの薬剤の反応による中毒ガスの発生も考えにくかった。長期保管した農薬から硫化水素が発生するならば同様の事故は今後も起こりうることになり，その発生機序について検討した。Fig. 1に瓶の内容として判読できたスリトーン 1，サプロール 2および代表的なカーバメート系殺虫剤であるマネブ 3の構造式を示す。スリトーンおよびサプロールの主成分であるトリホリンはいずれも硫黄基（S基）を含まず，これらが変化しても硫化水素は発生しないと考えられた。 The bottles contained old agricultural chemicals, and the discolored labels read the names of ingredients such as Saprol (fungicide) and Thritone (growth inhibitor). Neither includes a sulfur group. Example of carbamate drugs (Maneb). Maneb includes sulfur group. 今回の小瓶の主成分はカーバメート系殺虫剤と考えられ，Fig. 1の構造式に示すようにこれは硫黄基を含んでいる。Fig. 2にカーバメート系殺虫剤が分解，酸化されて発生したと考えられるイミダゾリジンチオンの構造式を示す。これにも硫黄基が含まれる。以上よりFig. 2に示すごとくカーバメート系殺虫剤が長期放置され，経年変化によりイミダゾリジンチオンに分解，酸化され，硫黄基を含むイミダゾリジンチオンがさらに分解され硫化水素が発生したと考えられた。 Imidazolidinethione: chemical name, molecular formula and structural formula. The carbamate drug left for a long period was decomposed into imidazolidinethione and was oxidized under secular change, and the produced imidazolidinethione having a sulfur group was further decomposed to generate hydrogen sulfide. カーバメート系殺虫剤から分解，酸化により生成されたイミダゾリジンチオンは通常は固形の物質で，常温では気化しないアミン臭のある物質である 4。工業用として塩素含有ゴム，とくにポリクロロプレン，クロロスルホン化ポリエチレン用加硫促進に使用されるもので通常農薬に使用される薬物ではない。これによる有害事象は接触性皮膚炎程度であり，意識障害，痙攣などの急性毒性は報告されていない。我々は症例報告やカーバメート系殺虫剤がどのような条件（年数，温度，圧力等）でイミダゾリジンチオンに変化するかなどの研究報告を検索したが見当たらなかった。また科学捜査研究所に改めて情報提供を依頼したがイミダゾリジンチオンに関する情報はなかった。イミダゾリジンチオンがさらに分解されて硫化水素が発生し，状況，症状からも高濃度の硫化水素に暴露された可能性が高い。後日，傷病者に今回の小瓶の放置期間について確認したが，本人もいつからあったのか不明とのことであった。カーバメート系殺虫剤以外の他の農薬に関しても，硫黄基（S基）を含めば，経年変化により硫化水素が発生する可能性は考えられる。 硫化水素（H2S）は無色の気体で腐卵臭のある無機化合物であり，肺や消化管粘膜から速やかに吸収される 5, 6。近年，硫化水素を発生させ自殺を図る事件が多数発生しており社会問題ともなった。石灰硫黄合剤の誤飲により硫化水素が発生し，急性中毒を引き起こすこともある 7。硫化水素は細胞内ミトコンドリアに存在するチトクローム酸化酵素と可逆的に結合することで組織での酸素の取り込みを阻害し，細胞呼吸を障害して低酸素症，中枢神経系細胞の直接障害を引き起こす 2。気道刺激が強い場合，暴露後24–72時間で肺水腫が出現することがあり，致死的暴露時は昏睡，呼吸抑制，振戦，複視，チアノーゼ，痙攣，頻脈が特徴的である 8。Table 2に硫化水素の濃度と身体への作用を示す。濃度が1,000ppmでは一呼吸以上でほぼ即死するとされ，ノックダウンと言われるくらい急激である 5。意識消失は脳幹の一時的な酸素欠乏のために生じると考えられる 9, 10。本症例では，おそらく500ppm以上の高濃度の硫化水素が小瓶より噴出したため，傷病者が一時的に意識消失，痙攣を来したものと考えられた。幸い発生した硫化水素の総量は少なかったため，肺水腫等の症状は見られなかったと思われる。本症例では硫化水素中毒に対する亜硝酸塩の投与などの治療は行わなかった。 また本症例では，当初救急隊からの情報では，小瓶から噴出したものが気体か液体かがはっきりせず，皮膚（眼）刺激症状があり，硫化水素と特定もできなかった。当直医は特定できない薬物中毒疑いとして病院着後，傷病者を脱衣し水除染を行った後，救急外来に収容した。硫化水素と特定できていれば脱衣，乾的除染で良いと考えられた。 救急隊の対応として，硫黄臭があり意識障害，痙攣を来した傷病者への接触に対して，より初期からの薬物中毒を念頭においた対応が求められる。状況把握で薬物噴出を確認しており，傷病者の家族および救急隊員の安全についてより配慮し，家族も搬送するべきであったかもしれない。受け入れ側の医師としても病院における2次災害の予防やメディカルコントロールとして近隣災害の可能性を指示できたかもしれない。 今回長期に保存した農薬瓶より発生した硫化水素による意識消失を来した1例を経験した。長期に農薬等を保管，放置すると，保管の状況によっては偶発的に硫化水素等の中毒物質が発生することもあり，その扱いには十分注意をするべきである。市民には農薬等を長期保管しないよう注意喚起が必要である。また救急の現場においては，中毒物質による意識障害にも注意して傷病者への接触を図ることが2次災害の防止の観点からも重要である。 本症例の要旨は，第42回日本救急医学会総会・学術集会（2014，福岡）にて発表した。 なお本論文に関し利益相反はない。

Quantitative and structural analyses of hazardous elements in Chinese medicines and herbs

ABSTRACTThirty samples of Chinese medicines and herbs were analyzed using instrumental neutron activation analysis (INAA) and X-ray diffraction (XRD) methods, mainly noting on the hazardous elements arsenic (As), mercury (Hg), chromium, antimony and cobalt. The three Niuhuang Jiedu Pian samples contained 8.6%, 8.3% and 2.2% As. Two out of four Liushen Wan samples contained approximately7% of both As and Hg. Despite being identically named, the other two Liushen Wan samples did not contain such high concentrations. Japanese Liushen Wan for children contained 1.2 ± 0.03% As and 31 ± 12 mg/kg Hg, whereas Liushen Wan for adults manufactured by another Japanese company contained 550 ± 22 mg/kg As and 1.2 ± 0.05 mg/kg Hg. All the chemical structural formulas of As and Hg in the high-concentration Niuhuang Jiedu Pian and Liushen Wan were realgar (As4S4), uzonite (As4S5) and cinnabar (HgS). Although the human body is generally not believed to absorb sulphides, continuous intake of these Chinese medicines is potentially no good because it is possible that some arsenic-sulfides will dissolve in gastric acid and then alter their chemical structures. Additionally, many herbs contained low concentrations of Hg, and their chemical structures were unknown.

Integrated interactive chart as a tool for teaching metabolic pathways.

An interactive chart of energy metabolism with didactic function, complementary to the already existing metabolic maps, located at the URL www.metpath.teithe.gr is being presented. The chart illustrates the major catabolic and biosynthetic pathways of glucose, fatty acids, and aminoacids, individually as well as in an integrated view. For every metabolite and reaction an information sheet may be presented at the side of the map as fancybox, containing chemical structural formulae, an external link to the KEGG database and links that lead to the reactions at which the produced metabolites may participate as reactants. The latter allows the user to navigate through metabolic reactions following a route similar to the metabolic flow of substances, while keeping track of the occurring chemical transformations. Simultaneously, users may observe how they move across the metabolic map, possibly along different pathways, thus enhancing the user's integrated perception of metabolism. The site has already been introduced in biochemistry lectures and the students evaluated it. Most students were helped a lot or more to understand individual pathways as well as their interconnections and they also found it pleasant and easy to navigate. The vast majority of the students considered its use in the classroom desired. The chart currently may be displayed in English and in Greek while more languages can be integrated in the future. The authors' view, in accordance to the users' perception, is that the presented site may offer biochemistry tutors and students a useful teaching aid.