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Selective kinetic determination of paraquat using long-wavelength fluorescence detection.

The reaction between paraquat, ascorbic acid, and Cresyl Violet in alkaline medium and in the presence of sodium dodecyl sulfate has been applied for the first time to the development of a kinetic-fluorometric method for the determination of paraquat. The reaction rate of this system is measured by using the stopped-flow mixing technique, which makes the method applicable to automatic routine analysis. Analytical data are obtained in approximately 30 s. The calibration graph is linear over the range 6-500 ng mL(-)(1), and the detection limit is 1.8 ng mL(-)(1). The relative standard deviation is <3%. The use of dynamic measurements at long wavelength favors the high selectivity of the method. Diquat behaves in this system similarly to paraquat, but its interferent effect is easily avoided by using cysteine. The proposed method has been applied to the determination of paraquat in tap water, milk, and white wine samples with recoveries of 89-104%.

Animals↗

Total synthesis and biological evaluation of Amaryllidaceae alkaloids: narciclasine, ent-7-deoxypancratistatin, regioisomer of 7-deoxypancratistatin, 10b-epi-deoxypancratistatin, and truncated derivatives.

Biocatalytic approaches have yielded efficient total syntheses of the major Amaryllidaceae alkaloids, all based on the key enzymatic dioxygenation of suitable aromatic precursors. This paper discusses the logic of general synthetic design for lycoricidine, narciclasine, pancratistatin, and 7-deoxypancratistatin. Experimental details are provided for the recently accomplished syntheses of narciclasine, ent-7-deoxypancratistatin, and 10b-epi-deoxypancratistatin via a new and selective opening of a cyclic sulfate over aziridines followed by aza-Payne rearrangement. The structural core of 7-deoxypancratistatin has also been degraded to a series of intermediates in which the amino inositol unit is cleaved and deoxygenated in a homologous fashion. These truncated derivatives and the compounds from the synthesis of the unnatural derivatives have been tested against six important human cancer cell lines in an effort to further develop the understanding of the mode of action for the most active congener in this group, pancratistatin. The results of the biological activity testing as well as experimental, spectral, and analytical data are provided in this manuscript for all relevant compounds.

Alkaloids↗

Structure assignment, total synthesis, and evaluation of the phosphatase modulating activity of glucolipsin A.

The previously unknown stereostructure of glucolipsin A (1), a complex glycolipid endowed with glucokinase-activating properties, was unambiguously elucidated as (2R,2'R,3S,3'S) by comparison of its spectroscopic and analytical data with those of all conceivable C(2)-symmetric stereoisomers. This set of macrodiolides was prepared by a sequence comprising auxiliary guided aldol reactions, glycosidation of the resulting beta-hydroxy acid derivatives with trichloroacetimidate 7, followed by hydrolytic cleavage of the auxiliaries used. The hydroxy acids thus formed were subjected to a macrodilactonization reaction mediated by 2-chloro-1,3-dimethylimidazolinium chloride (22) as the activating agent; this transformation is highly productive only in the presence of admixed potassium cations which likely serve as templates to preorganize two substrate molecules in a favorable head-to-tail arrangement. Glucolipsin and analogues were subjected to enzymatic assays that revealed that glycoconjugates of this type effectively inhibit the activity of the dual specific phosphatase Cdc25A with IC(50) values in the low micromolar range, while being hardly active against the tyrosine phosphatase PTP1B in vitro. This activity profile was compared to that of other glycolipids previously prepared in this laboratory, including cycloviracin B(1) (2), caloporoside (38), woodrosin I (39), sophorolipid lactone (40), and tricolorin G (41).

Disaccharides↗

IB-01212, a new cytotoxic cyclodepsipeptide isolated from the marine fungus Clonostachys sp. ESNA-A009.

IB-01212, a new cytotoxic cyclodepsipeptide featuring C2 symmetry, was isolated from the mycelium extract of Clonostachys sp. ESNA-A009. The amino acid sequence of the compound was determined by spectroscopy techniques. The absolute configuration of the amino acids was determined by a combination of the Marfey and menthol methods. The structure, which was confirmed by comparison of the analytical data for the natural product with a sample obtained by solid-phase peptide synthesis, was revealed to be a cyclic dimer formed by two chains of L-N,N-Me2Leu-L-Ser-L-N-MeLeu-L-N-MePhe bound by the two esters formed between the carboxylic acid of the L-N-MePhe and the hydroxyl function of the L-Ser. IB-01212 is highly cytotoxic to different tumor cell lines.

Antibiotics, Antineoplastic↗

Organized self-assembled monolayers from organosilanes containing rigid pi-conjugated aromatic segments.

The morphology of surfaces modified by pi-conjugated arylsilanes depends on various parameters such as the nature and the number of the hydrolyzable functions or the length of the aromatic segment. The grafting of phenyltrichlorosilane and phenyltrimethoxysilane leads to multilayers even when the reactions are carried out at 0 degrees C, the films obtained from phenyltrichlorosilane being much thicker than the one obtained from phenyltrimethoxysilane. A submonolayer is obtained using phenyltriethoxysilane. Whereas the trifunctional phenyltrichlorosilane forms an inhomogeneous multilayer, the difunctional phenyldichlorosilane (PhSiHCl2) and the monofunctional phenylchlorosilane (PhSiH2Cl) (the SiH bond is not reactive under these experimental conditions) deposit as dense homogeneous monolayers. For these two phenylchlorosilanes, the surface analytical data are similar except for contact angle measurements, which can be explained by a different orientation of the phenyl group at the surface. Concerning the influence of the length of the aromatic segment on the quality of the film, styryltrimethoxysilane and methylstilbenyltrimethoxysilane lead to dense monolayers indicating that adding a short group such as the vinyl group is sufficient to induce an organization between aromatic groups and to achieve a dense monolayer.

Journal Article↗

Profiling taxanes in Taxus extracts using lc/ms and lc/ms/ms techniques.

Analytical methodology developed for the trace analysis of natural products in crude extracts was utilized for the rapid and systematic structure elucidation of taxanes in Taxus extracts and process intermediates. This method integrates analytical hplc, uv detection, uv spectroscopy, full-scan ionspray mass spectrometry and tandem mass spectrometry on-line. The identification of structure of a taxane is based on comparing the mass spectrometric characteristics of the taxane with the paclitaxel substructural "template." Analytical data for taxanes in preparations from Taxus brevifolia and Taxus baccata were observed, including chromatographic characteristics using a standard hplc system, molecular weight, and collision induced dissociation (cid) tandem mass spectrometry (ms/ms) product ion spectra. The data obtained for 18 taxanes from natural sources using this method provided a taxane profile database useful for the rapid identification of taxanes in mixtures and samples of limited quantity.

Bridged Bicyclo Compounds↗

Identification of aminobiphenyl derivatives in commercial hair dyes.

A recent epidemiological study suggested that aromatic amines present in hair dyes may contribute to an increased risk of bladder cancer (Gago-Dominguez, et al. (2003) Carcinogenesis 24, 483-489). Moreover, a preliminary study linked frequent hair dye usage with elevated levels of DNA adducts of 4-aminobiphenyl (4-ABP) in human epithelial breast cells (Gorlewska, et al. Proc. Am. Assoc. Cancer Res. 43, 1018-1019). Therefore, we sought to determine if 4-ABP, a recognized human urinary bladder carcinogen, is present in commercial hair dyes. 4-ABP was isolated from dyes by solvent extraction with hexane, followed by silica gel chromatography, either with or without chemical treatment of the extract with Zinc/HCl, and a final purification with a mixed cation exchange reversed-phase resin. The identity of 4-ABP was confirmed by both HPLC with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and gas chromatography with negative ion chemical ionization mass spectrometry (GC-NICI-MS) following chemical derivatization with pentafluoropropionic anhydride (PFPA). The levels of 4-ABP ranged from not detectable (<0.29 parts per billion (ppb)) up to 12.8 ppb. The noncarcinogenic isomer 2-aminobiphenyl (2-ABP) was also found at quantities up to 310 ppb. 4-ABP was detected in eight of the 11 hair dyes and found in black, red, and blonde hair dyes but not in brown hair dyes. 1,4-Phenylenediamine (PPD) is a key constituent for color development of many permanent hair dyes. Some batches of chemical research grade PPD were contaminated with 4-ABP (up to 500 ppb) and 2-ABP (up to 70 parts per million) and may be a source of ABP contamination in hair dyes. These analytical data demonstrate that 4-ABP is present in some hair dyes. Studies on dermal absorption and bioavailability of 4-ABP from hair dyes are required to determine if this aromatic amine contributes to the increased risk of bladder cancer reported in frequent users of hair dyes.

Aminobiphenyl Compounds↗

Inherited defects of purine and pyrimidine metabolism: laboratory methods for diagnosis.

The diagnosis of the majority of the known inherited defects of purine and pyrimidine metabolism can be achieved by analysing urinary excretion profiles. A quantitative measurement of the urinary uric acid/creatinine ratio should be the first approach for purine defects. The general screening system involves separation of the bases and nucleosides by reversed-phase high-performance liquid chromatography and multiwavelength UV detection. The catabolic defects of pyrimidine degradation can be diagnosed by gas chromatography-mass spectrometry as used for organic acids. For the detection of adenylosuccinase deficiency, several simple but effective thin-layer chromatographic methods are available. Techniques such as liquid chromatography-mass spectrometry, direct nega-tiveion fast-atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy give promising results, but are not yet being used on a large scale. Patients should keep to a simple diet and preferably be free of medication in order to allow a reliable interpretation of the analytical data.

Animals↗

Comparative studies on the nutritional and toxic composition of three varieties of Lesianthera africana.

The research presents analytical data on three varieties of a commonly consumed vegetable, Lesianthera africana, in southern Nigeria. The Etoi (bitter) variety seemed to possess the best (p < or = 0.01) nutritional value (highest lipid, protein, calories, iron, calcium, phosphorus, least fiber) but highest toxic components (mg/100 g: 1.62 HCN; 17.6 oxalate; 1630 glucosinolates), which are far below toxic limits. The Ikot Abasi (riverine) variety was found to be highly (p < or = 0.01) fibrous (18.1 mg/100 g dry matter) but low in micronutrient minerals. The Etinan (flavorful) variety was found to be moderately nutritious. The findings are discussed in relation to nutrient interactions and recommendations are made regarding dietetic use.

Calcium↗

The contribution of nonmalignant tumors to CNS tumor incidence rates among children in the United States.

OBJECTIVES: According the U.S. National Cancer Institute (NCI), the incidence rate of primary malignant central nervous system (CNS) neoplasms among children is about 30 per million person-years. This rate, however, underestimates the true burden of CNS tumors because nonmalignancies are not included in the NCI case reporting system. Intracranial tumors, to an extent regardless of their histological behavior, can have a malignant clinical course and result in a high degree of morbidity and mortality. The purpose of this report is to estimate the contribution that nonmalignant tumors have on the overall incidence of CNS tumors in children. METHODS: Population-based data from the Central Brain Tumor Registry of the United States were analyzed. Included in the analysis were children aged 0-19 years who were diagnosed with a primary CNS tumor from 1990-93 (N = 1133). RESULTS: The inclusion of nonmalignancies increased the CNS tumor incidence rate by 28% from 29.4 to 37.6 per million person-years. The increases were 17% for children aged 0-4 years, 17% for children aged 5-9 years, 31% for children aged 10-14 years and 57% for adolescents aged 15-19 years. Differences in patterns between malignant and nonmalignant tumor occurrence by sex, histology, and location were also observed. CONCLUSION: Because of the potentially profound adverse health effects on children who experience CNS tumors, the systematic collection of both malignancies and nonmalignancies is consistent with the mission of public health surveillance. Without such population-based data, analytic epidemiologic studies to evaluate disease etiology and assess disease consequences are greatly hindered.

Adolescent↗

Correlations of trace element levels within and between different normal autopsy tissues analyzed by inductively coupled plasma atomic emission spectrometry (ICP-AES).

Imbalance in trace metal metabolism may lead to metal interactions that may be of patho-physiological importance. Knowledge of the relation between trace metals in normal tissues is needed to assess abnormal deviations associated with disease. In this study correlations between Cu, Co, Cr, Fe, Mn, Ni, Se, Zn, Al, Ba, Cd, Pb and Sr within the same and between 6 different, normal autopsy tissues were determined using Spearman rank correlation analysis based on analytical data obtained by inductively coupled plasma atomic emission spectrometry (ICP-AES). Fe-Co were correlated in most tissues. Cu-Mn, Zn-Cu, Zn-Mn and Zn-Cd were highly correlated in the kidney medulla. Ni-Ni, Sr-Sr and Cd-Cd were correlated between several tissues, while Fe-Fe, Zn-Zn and Cu-Cu were correlated between kidney cortex and medulla. Mn-Mn was highly correlated between the liver and brain front lobe, cerebellum and heart. High correlations were found for Ni-Co and for Se-Mn between the kidney cortex and brain front lobe and pancreas respectively. Inverse correlations were found for Se-Cd between kidney cortex and cerebellum, for Se-Cd and Cd-Zn between kidney medulla and heart, for Co-Sr and Fe-Sr between the liver and kidney cortex and heart respectively, and for Sr-Mn between kidney medulla and pancreas. A large number of trace elements are statistically correlated within and between different, normal tissues. Knowledge of these correlations may contribute to increase the understanding of kinetic interactions of trace metals in the body and the role of such interactions in normal and disturbed trace metal metabolism.

Adolescent↗

PCB congener distribution in estuarine water, sediment and fish samples: implications for monitoring programs.

Traditional analyses for PCBs in environmental matrices have focused on commercial Aroclor mixtures with detection limits in the 100 to 1000 part per trillion range. This approach has recently been supplanted by analyses for specific PCB compounds called congeners with detection limits less than 0.5 ppt. At the national level, total PCB determinations based upon selected PCB congeners typically characterize analyses of surface water, sediment and tissue. These federal efforts rely on a suite of 18 to 20 congeners out of a total of 209 congeners to characterize total PCB. The present study compares total PCB estimates based upon this subset of congeners with estimates based upon an expanded list of 81 congeners from water, sediment and fish tissue collected from the Delaware Estuary. Analytical data from monitoring programs conducted in the Delaware Estuary by the Delaware River Basin Commission, NOAA National Ocean Service, U.S. Army Corps of Engineers and the U.S. Environmental Protection Agency from 1996 to 1998 were evaluated. Total PCB estimates derived from the different sets of congeners, including the adjustment factor of 2.0 used by NOAA, were compared. This evaluation indicated that differences exist between total PCB determinations based upon these approaches, and that these differences vary depending on the matrix analyzed. The bias associated with using a smaller set of PCB congeners, and the implications for risk assessment are discussed.

Animals↗

Fairweather and ESID: contemporary impact and a legacy for the twenty-first century.

This paper illustrates how the articles in this special issue demonstrate the central values, research, and action principles inherent in Fairweather's ESID model. The programs described in these articles address earlier social problems in new forms (e.g., previously, institutionalized mentally ill patients and now, the homeless mentally ill) and new issues (e.g., HIV prevention). Dissemination of innovative programs is abundant, but only recently has research begun in earnest to study the critical processes of dissemination. Moreover, Fairweather has pointed us in important, but yet unrealized directions for how to pursue a theory of social change on the basis of ecological concepts, innovative research methods and data analytic techniques, and salient change agent behaviors and principles.

Diffusion of Innovation↗

The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica.

Salmochelins represent novel carbohydrate containing catecholate siderophores, which are excreted by Salmonella enterica and uropathogenic Escherichia coli strains under low-iron stress. While previous analytical data showed salmochelins to contain 2,3-dihydroxybenzoyl-L-serine and glucose, the molecular structure remained elusive. Structure elucidation with electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), GC-MS and 2D-NMR now revealed that salmochelins are enterobactin-related compounds, which are beta-C-glucosylated at the 5-position of a 2,3-dihydroxybenzoyl residue. The key compound salmochelin S4 is a twofold beta-C-glucosylated enterobactin analogue. Comparison of partial structures of salmochelin with a C-glycosylated compound previously characterized by another group strongly suggest that salmochelins represent the long sought compounds termed Salmonella resistance factors (SRF) or pacifarins. Transformation of iro-genes into enterobactin-producing E. coli K12 confers the ability to produce salmochelins. A detailed analysis proved iroB to be the sole gene with glycosyltransferase activity necessary for salmochelin production. Salmochelins compared to enterobactin are the better siderophores in the presence of serum albumin. This may indicate for salmochelins a considerably more important role for pathogenic processes in certain Escherichia coli and Salmonella infections than formerly assigned to enterobactin. This conclusion is supported by the location of the iro genes on pathogenicity islands of uropathogenic E. coli strains.

Chromatography, High Pressure Liquid↗

Interactions between toxic (As, Cd, Hg and Pb) and nutritional essential (Ca, Co, Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements in the tissues of cattle from NW Spain.

Since the toxicity of one metal or metalloid can be dramatically modulated by the interaction with other toxic or essential metals, studies addressing the chemical interactions between trace elements are increasingly important. In this study correlations between the main toxic (As, Cd, Hg and Pb) and nutritional essential (Ca, Co, Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements were evaluated in the tissues (liver, kidney and muscle) of 120 cattle from NW Spain, using Spearman rank correlation analysis based on analytical data obtained by ICP-AES. Although accumulation of toxic elements in cattle in this study is very low and trace essential metals are generally within the adequate ranges, there were significant associations between toxic and essential metals. Cd was positively correlated with most of the essential metals in the kidney, and with Ca, Co and Zn in the liver. Pb was significantly correlated with Co and Cu in the liver. A large number of significant associations between essential metals were found in the different tissues, these correlations being very strong between Ca, Cu, Fe, Mn, Mo and Zn in the kidney. Co was moderately correlated with most of the essential metals in the liver. In general, interactions between trace elements in this study were similar to those found in polluted areas or in experimental studies in animals receiving diets containing high levels of toxic metals or inadequate levels of nutritional essential elements. These interactions probably indicate that mineral balance in the body is regulated by important homeostatic mechanisms in which toxic elements compete with the essential metals, even at low levels of metal exposure. The knowledge of these correlations may be essential to understand the kinetic interactions of metals and their implications in the trace metal metabolism.

Aging↗

Comparison and analysis of the complete nucleotide sequence of foot-and-mouth disease viruses from animals in Korea and other PanAsia strains.

During the last 3 years, foot-and-mouth disease virus serotype O, named PanAsia, caused two outbreaks in the Republic of Korea. To determine if there was an obvious genetic relationship between the virus isolated in 2002 (O/SKR/2002) and the O/SKR/2000, and to further analyze the epidemiological relationships between the PanAsia viruses and the viruses identified in Korea, the complete nucleotide sequence of the O/SKR/2002 and the O/SKR/2000 were determined by automatic cycling sequencing and primer walking. The nucleotides and the deduced amino acid (aa) sequences of the strains identified in Korea were compared with each other and also those enrolled in the GenBank database. In comparison and analysis of the viruses identified in Korea, any deletions or insertions in the specific fragment gene of both the O/SKR/2002 and O/SKR/2000 were not identified. However, comparison of the aa sequence of the identified virus in 2002 from pigs with those of other PanAsia strains revealed significant substitutions of 4 aa in the VPI region and 8 aa in the 3A region. In phylogenetic analysis based on the translated region, the identified virus in 2002 appeared to be the divergence of approximately 1% degree with other PanAsia viruses. Also, animal experiments indicated that O/SKR/2000 is not host-restricted and develop the clinical signs in the main susceptible livestock species (cattle and pigs). However, O/SKR/2002 did not develop the clinical signs in cattle and showed severe clinical signs only in pigs. These analytic data suggest that 2002 outbreaks in Korea is not re-occurred but re-introduced from nowhere.

Amino Acid Sequence↗

The apo A-I gene promoter region polymorphism determines the severity of hyperlipidemia after heart transplantation.

BACKGROUND: To study whether the Apolipoprotein A-I (apo A-I) promoter region gene polymorphism produces changes in the lipid profile of heart transplant recipients. METHODS: One hundred and three heart transplant recipients (93 men and 10 women, with a mean age of 47 +/- 13 yr) receiving triple immunosuppressive therapy were submitted to a genetic study of the apo A-I gene promoter region. Anthropometric and analytical data, including lipid profile, arterial blood pressure, were collected prior to transplantation and 3, 6, 12, and 24 months after transplantation. RESULTS: Sixty-three subjects had the GG genotype and 40 the GA genotype. Carriers of the GA genotype had higher triglyceride levels at 6 months and 2 yr (2.50 +/- 1.20 versus 1.93 +/- 0.98 mmol/L and 2.46 +/- 1.58 versus 1.60 +/- 0.68 mmol/L, respectively, p < 0.001), and a greater rise in LDL-cholesterol at 1 yr than the GG subjects (4.57 +/- 1.16 versus 4.16 +/- 1.18 mmol/L, p < 0.05). Multiple regression analyses showed that genetic variants at the apo A-I promoter region are responsible for 11% of the variability in triglyceride levels at 6 months (p = 0.005). CONCLUSIONS: The GA genotype of the apo A-I promoter region produces a greater rise in plasma triglyceride and LDL-cholesterol levels in heart transplant patients.

Apolipoprotein A-I↗

Introduction to the special section on structural equation modeling.

Structural equation modeling (SEM) is a frequently used data-analytic technique in psychopathology research. This popularity is due to the unique capabilities and broad applicability of SEM and to recent advances in model and software development. Unfortunately, the popularity and accessibility of SEM is matched by its complexities and ambiguities. Thus, users are often faced with difficult decisions regarding a variety of issues. This special section is designed to increase the effective use of SEM by reviewing recently developed modeling capabilities, identifying common problems in application, and recommending appropriate strategies for analysis and evaluation.

Humans↗