This study aimed to examine the side effects of selected neonicotinoids (Acetamiprid, Aceta, and Imidacloprid, Imid) on Oreochromis niloticus juveniles. The acute toxicity, Probit method, revealed an LC50 of 195.81 and 150.76 ppm for Aceta/96 h and Imid/72 h respectively. The fish were divided into three groups that were exposed, for 21 days (n = 5/replicate), to 1/10 of the LC50 of either neonicotinoids, however, the third was an unexposed control group. Results of erythrocytic micronucleus (MN), and nuclear abnormalities (NA) showed that Aceta and Imid exposure caused a significant (p < 0.05) increase in MN by ~ 2.2 and ~ 10 folds, respectively relative to control. NAs occurred at the order of kidney-shaped > budding > binucleated in Aceta, however, budding > binucleated > kidney-shaped was noticed in the Imid group. Histopathological changes in gills, liver, and muscles were observed significantly in both exposed groups with more severity in the Imid group. Collectively, Aceta and Imid have potential genotoxicity and histopathological alterations in O. niloticus.

Lactobacillus plantarum is considered a potential probiotic supplementation for treating obesity. However, the underlying molecular mechanism is poorly understood. Our previous study displayed that L. plantarum FRT4 alleviated obesity in mice fed a high-fat diet (HFD) through ameliorating the HFD-induced gut microbiota dysbiosis. To explore the roles of FRT4 in obesity prevention, in this study, we investigated changes in serum metabolomic phenotype by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) and analyzed the pathway of HFD-fed Kunming female mice orally administered with FRT4 for eight weeks. Using orthogonal partial least squares discriminant analysis (OPLS-DA), metabolite patterns with significant changes were observed. 55 metabolites including phosphatidylcholine, lysophophatidylcholine, sphingomyelin, serotonin, indole-3-methyl aceta, indole-3-carbinol, indole-5,6-quino, 11,12-DHET, prostaglandin B2, leukotriene B4, and 3-hydroxybenzoic acid were identified as potential biomarkers associated with obesity, which were mainly involving in glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. Perturbations of 14 biomarkers could be regulated by FRT4 intervention. These metabolites may serve as valuable biomarkers to understand the mechanisms by which intake of diets containing FRT4 contributes to the treatment or prevention of obesity. Thus, FRT4 can be a promising dietary supplement for the prevention of HFD-induced obesity.

On juveniles of Oreochromis niloticus, the protective potential of ascorbic acid (Asc) against oxidative stress and genotoxicity induced by acetamiprid (Aceta) sub-lethal concentrations was investigated in this study. Fishes were divided into six groups and exposed to either Asc (50 ppm), 10 and 20 ppm Aceta, 10 ppm (Aceta)+Asc, 20 ppm (Aceta)+Asc, or the unexposed control group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities and their transcripts were assessed. DNA damage in erythrocytes, hepatocytes, and gill cells, in addition to the mitotic index (MI), and the existence of erythrocytic nuclear abnormalities (ENAs) were performed. The results showed that concentrations of Aceta (10 and 20 ppm) induced oxidative stress by altering the antioxidant enzyme activities and transcripts. There were genotoxic effects of Aceta exposure showed by the significant (P < 0.05) increase in DNA-damaged cells and ENA, meanwhile a decrease in MI. Co-exposure with Asc showed significant alleviations of oxidative status and genotoxicity. Thus, results suggest that Asc-combined exposure could be the effective treatment against Aceta-induced oxidative stress accompanied with genotoxicity in O. niloticus.

Diffraction patterns observed in surface plasmon resonance imaging (SPRI) microscopy measurements of single gold nanorods (AuNRs) exhibit a complex behavior at wavelengths near the longitudinal plasmonic resonance band. SPRI microscopy measurements at 814 nm from AuNRs in three samples with resonance extinction maxima at 670, 816, and 980 nm reveal a variety of diffraction patterns with central peaks that are either positive, negative, or biphasic. A unitless ratio parameter MR (-1 ≤ MR ≤ 1) is created to describe the distribution of diffraction patterns. A purely negative (MR = -1) central peak is observed for 30%, 57%, and 98% of the diffraction patterns in the 670, 816, and 980 nm samples, respectively. These results along with a theoretical modeling of the diffraction patterns with an anisotropic complex scattering coefficient suggests that this behavior only occurs for AuNRs when the laser wavelength used in SPRI experiments is shorter than the AuNR plasmonic resonance maxima, that is, in the anomalous dispersion region.

Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 to accelerate the development of new drugs for neuroblastoma. Advances have occurred, with eight of nine high-priority targets being evaluated in paediatric trials including anaplastic lymphoma kinase inhibitors being investigated in front-line, but significant challenges remain. This article reports the conclusions of the second NDDS forum, which expanded across the Atlantic to further develop the initiative. Pre-clinical and clinical data for 40 genetic targets and mechanisms of action were prioritised and drugs were identified for early-phase trials. Strategies to develop drugs targeting TERT, telomere maintenance, ATRX, alternative lengthening of telomeres (ALT), BRIP1 and RRM2 as well as direct targeting of MYCN are high priority and should be championed for drug discovery. Promising pre-clinical data suggest that targeting of ALT by ATM or PARP inhibition may be potential strategies. Drugs targeting CDK2/9, CDK7, ATR and telomere maintenance should enter paediatric clinical development rapidly. Optimising the response to anti-GD2 by combinations with chemotherapy, targeted agents and other immunological targets are crucial. Delivering this strategy in the face of small patient cohorts, genomically defined subpopulations and a large number of permutations of combination trials, demands even greater international collaboration. In conclusion, the NDDS provides an internationally agreed, biologically driven selection of prioritised genetic targets and drugs. Improvements in the strategy for conducting trials in neuroblastoma will accelerate bringing these new drugs more rapidly to front-line therapy.

The antioxidant protective properties of polyaromatic organic layers were evaluated toward reactive oxygen species (ROS) using scanning electrochemical microscopy in a foot-printing strategy. The layers were prepared by electrografting of aryldiazonium salts. Where p-(methyl)phenyl films show only weak protective properties toward ROS, p-(ethynyl)phenyl films evidence efficient protection of the covered surfaces. Applied potentials and electrolytes used during oxygen reduction reaction are critical parameters to control, prevent, or reduce the influence of ROS production and hence enhance the device lifetime.

For the purpose of preparing well-organized functional surfaces, carbon and gold substrates were modified using electroreduction of a tetrahedral-shape preorganized tetra-aryldiazonium salt, leading to the deposition of ultrathin organic films. Characterization of the modified surfaces has been performed using cyclic voltammetry, X-ray photoelectron spectroscopy, infrared absorption spectroscopy, ellipsometry, atomic force microscopy, and contact angle measurements. The specific design of the tetra-aryldiazonium salts leads to an intrinsic structuring of the resulting organic films, allowing molecular sieving and current rectification properties toward redox probes in solution.

The title compound, [Ge2(C8H17N2)4O2], crystallizes with imposed twofold symmetry, which allows the monodentate amidinate ligands to be arranged in a cisoid fashion. The independent Ge-O distances within the central Ge2O2 ring, which is essentially planar (r.m.s. deviation = 0.039 Å), are 1.7797 (8) and 1.8568 (8) Å. The germanium centres adopt a distorted trigonal-bipyramidal geometry, being coordinated by the two O atoms and by one bidentate and one monodentate amidinate ligand (three N atoms). One N-isopropyl group is disordered over two positions; these are mutually exclusive because of 'collisions' between symmetry-equivalent methyl groups and thus each has 0.5 occupancy.

Sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is a devastating pest that can cause severe damage to a range of crops by direct feeding and by plant virus transmission. Because of indiscriminate use of insecticides, this whitefly has developed resistance to several insecticides, including neonicotinoids. Our objectives were to determine fitness components affected by acetamiprid resistance in B. tabaci. Assay results showed that selection with acetamiprid had removed heterozygotes from the field population because the survival rate of the resistant population was significantly greater than that of the field population at a very high dose. Comparison of various life traits between the acetamiprid-selected (Aceta-SEL) population and three other populations showed that the numbers of eggs laid by acetamiprid Aceta-SEL population were significantly lower compared with that of other populations but that the proportions of eggs hatched were significantly higher. However, the time taken by nymphal stages of the Aceta-SEL population to develop was significantly higher than that of the susceptible populations. The intrinsic rate of increase, net reproductive rate, mean generation time, and doubling time of Aceta-SEL was significantly higher than Lab-PK and UNSEL populations, but the growth index was similar for all populations. The growth index and high intrinsic value of Aceta-SEL population suggest that the resistance allele may not have detrimental impact. The lack of fitness costs in B. tabaci could promote the rapid development of resistance to acetamiprid and other neonicotinoids. This resistance could threaten the sustainability of whitefly management program on genetically engineered cotton (Gossypium hirsutum L.) where neonicotinoids are being sprayed to manage sucking pests in the field.

In order to generate hybrid antimicrobial remedies with novel mode of action, two series of quinoline based 1,3,4-oxadiazole derivatives condensed with N-aryl/benzothiazolyl acetamides were synthesized and the MIC values of the compounds towards eight reference bacterial strains (S. aureus, B. cereus, E. coli, P. aeruginosa, K. pneumoniae, S. typhi, P. vulgaris, S. flexneri), four fungi (A. niger, A. fumigatus, A. clavatus, C. albicans) and Mycobacterium tuberculosis H37Rv were assayed in vitro. Quinoline-6-carboxlic acid was treated with thionyl chloride in refluxing methanol to obtain the corresponding ester derivative to be hydrazinolyzed by 99% hydrazine hydrate in ethanol to produce carbohydrazide intermediate. The carbohydrazide precursor underwent cyclization by carbon disulfide and ethanolic KOH to construct 5-quinolinyl-6-yl-1,3,4-oxadiazol-2-thiol. Substituted 2-chloro-N-phenyl(benzothiazolyl)aceta-mide derivatives were then condensed to 1,3,4-oxadiazole nucleus via sulphur linkage to yield the desired products. Target products bearing N-benzothiazolyl-2-chloroacetamides displayed good inhibitory potential. The biological screening identified that many final analogues exhibited a significant inhibition of the growth of microorganisms at 3.12-25 μg/mL of MIC, which were comparable to control drugs. The influence of the presence of various functional groups to the phenyl/benzothiazolyl ring on activity profiles was investigated. The proposed structures of the newly prepared products were confirmed with the aid of IR, 1H NMR, 13C NMR spectroscopy and elemental analysis. These results may provide new insights in the design of a novel pool of bioactive templates.

In this study, the amounts of odorous carbonyl compounds (OCCs) including acetaldehyde (Acet-A), propionaldehyde (Pron-A), butylaldehyde (Buty-A), iso-valeric aldehyde (Iso-Vale-A) and n-valeric aldehyde (N-Vale-A) emitted from a fishery industrial complex near the exhibition facilities of "Expo 2012 Yeosu Korea" were measured. Acet-A was found to be the most abundant OCC, and the total concentrations of the OCCs were the highest in the summer. However, due to vehicular exhaust and photochemical reactions, the concentrations of some of the OCCs presented their highest levels in the fall. A significant correlation between Acet-A and Buty-A was found at the major fishery facilities (r = 0.816, p = 1.87E-15, n = 60) and at the border areas (r = 0.809, p = 3.40E-12, n = 48) of this fishery industrial complex. The concentrations of OCCs at the border areas were not worse than those at the urban areas in other places, indicating that the concentrations of ambient OCCs at the border areas were not greatly influenced by manmade activities.

Bioassays (at generation G2) with a newly collected field population (designated CH4) of Plutella xylostella (L.) (Lepidoptera: Plutellidae) from farms in the Cameron Highlands, Malaysia, indicated resistance to acetamiprid, deltamethrin, lambda-cyhalothrin, and esfenvalerate. At G3, the field-derived population was divided into two subpopulations, one subpopuplation was selected (G3 to Go10) with acetamiprid (aceta-SEL), whereas the second subpopulation was left unselected (UNSEL). A significant reduction in the resistance ratio for each compound was observed in UNSEL at G,1, indicating that the observed resistance to each insecticide was unstable. For aceta-SEL, bioassays at G,, found that selection with acetamiprid gave a resistance ratio of 409 compared with UNSEL. The LC50 values for deltamethrin, lambda-cyhalothrin, and esfenvalerate to aceta-SEL were similar at both G11 and G2. This suggests that acetamiprid selection maintained the otherwise unstable resistance to these compounds in the aceta-SEL population. Logit regression analysis of F1 reciprocal crosses between aceta-SEL and the susceptible Lab-UK indicated that resistance to acetamiprid was inherited as an autosomal, incompletely recessive (DLC = 0.26) trait. Tests of monogenic inheritance and weight distribution suggested that resistance to acetamiprid was controlled by a single locus.

As demonstrated in previous studies, both cyclooxygenases (COXs) and nitric oxide synthases (NOS) localized peripherally and/or centrally participate in the antinociceptive action of acetaminophen (ACETA). We showed that opioidergic system(s) was involved in the mechanism of ACETA action, as well. In previous and recent studies, the changes in nociceptive threshold were estimated using a mechanical and chemical stimulus. In this study, the influence of nonspecific inhibitor of NOS [N(G)-nitro-L-arginine (L-NOArg)] on antinociceptive action of ACETA administered icv and it was studied in rats. ACETA increased threshold for electrical stimuli, however, its analgesic activity was not dose-dependent. Independently of the route of administration, the existence of a ceiling dose of ACETA was observed above which the activity of ACETA was self-limited. Pretreatment with L-NOArg (ip) markedly increased the action of higher doses of ACETA. It suggests that the attenuation of analgesic action of higher doses of ACETA may be due to increased activity of NOS.

The influence of naloxone (NAL), a competitive antagonist of mu, kappa, delta and sigma receptors; D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP), selective antagonist of mu-opioid receptors; nor-binaltorphimine (NOR-BNI), a potent and higly selective kappa opioid receptor antagonist; naltrindole (NTI), a delta-opioid receptor antagonist and naltriben (NTB), a highly selective delta(2)-opioid receptor antagonist on antinociceptive action of acetaminophen (ACETA) was studied in rats. NAL administered intraperitoneally (ip) or intracerebroventricularly (icv), and CTOP and NOR-BNI administered icv, markedly decreased the antinociceptive activity of the high dose of ACETA (400 mg/kg). Pretreatment with NTI (sc), as well as with naloxone (it), and NTB (it) slightly but significantly attenuated the ACETA antinociception. The possible involvement of the opioidergic systems in antinociceptive activity of ACETA is discussed.

As it has been demonstrated in a previous study, both cyclooxygenases (COXs) and nitric oxide synthases (NOSs) participate in the mechanism of acetaminophen (ACETA) action. Results obtained in this study indicate that intrathecal (it) or intracerebroventricular (icv) pretreatment with LG-nitro-L-arginine (L-NO-Arg), a non-selective inhibitor of NOS activity, as well as with 7-nitroindazole (7-NI), a selective nNOS inhibitor, potentiated the antinociceptive activity of subceiling doses of ACETA, but were without effect on the action of supramaximal doses in Randall-Selitto test. Similar effect of L-NO-Arg and 7-NI it was observed in writhing test, whereas L-NO-Arg icv or L-NIL it did not influence the action of ACETA in this model. Indomethacin (IND), an inhibitor preferentially acting on COX-1, as well as nimesulide (NIM) and celecoxib (CECOX), i.e. preferential and selective inhibitor of COX-2, respectively, administered icv almost completely blocked the antinociceptive effect of ACETA in Randall-Selitto method. On the other hand, pretreatment with NSAIDs it initially increased and then attenuated the ACETA antinociception. Yohimbine (YOH), an alpha2-adrenergic receptor antagonist, did not modify the antinociceptive action of ACETA administered alone. However, YOH decreased the nociceptive threshold increased by simultaneously administered IND and ACETA, NIM and ACETA, as well as CECOX and ACETA in Randall-Selitto model. In contrast to the peripheral (sc) application, IND administered centrally (icv or it) did not modify the ACETA antinociception in writhing test. Neither NIM nor CECOX administered sc, it or icv changed the ACETA antinociception in this model. Possible mechanisms and sites of antinociceptive effects of ACETA are discussed.

The influence of cyclooxygenase (COX) and NO synthase inhibitors on antinociceptive action of acetaminophen (ACETA) was studied in rats. ACETA increased the nociceptive threshold for both mechanical (Randall-Selitto test) and chemical stimuli (writhing test). In both models the existence of ceiling dose of ACETA was observed. Indomethacin (IND), an inhibitor preferentially acting on COX-1, as well as nimesulide (NIM) and celecoxib (CECOX), i.e. respectively preferential and selective inhibitors of COX-2, markedly decreased the antinociceptive activity of ACETA in Randall-Selitto test. In contrast, IND increased, whereas both NIM and CECOX did not have any effect on ACETA action in writhing test. Pretreatment with LG-nitro-L-arginine (L-NO-ARG), an unspecific inhibitor of NO synthase, 7-nitroindazole (7-NI), relatively specific inhibitor of neuronal NO synthase, and L-N6(1-iminoethyl)lysine (L-NIL), relatively selective inhibitor of inducible NO synthase, significantly increased the action of the lower doses of ACETA (50 and 100 mg/kg) in writhing test, whereas it did not modify the effects of the higher doses. Similar effect of L-NO-ARG and 7-NI was observed in Randall-Selitto test, whereas L-NIL did not influence the action of ACETA. The possible involvement of COX and NO synthase systems in antinociceptive activity of ACETA is discussed.

Four most common brands of paracetamol (4-aceta-midophenol) tablets were examined for the changes in their disintegration properties after inoculation with Staphylococcus aureus, Bacillus cereus, Klebsiella aerogenes and Pseudomonas aeruginosa and incubating for 5 weeks. The disintegration times varied from one brand to the other, reaching maximum values of 72 min., 82 min., 110 min. and 120 min. for S. aureus, B. cereus, P. aeruginosa and Klebsiella aerogenes, respectively. All brands of paracetamol tablets revealed the presence of cotton wool-like fibrils which were seen to be interwoven within the tablets' matrices and these were believed to have caused the higher disintegration times.

The intracranial effects of acetazolamide on flow velocities can be monitored noninvasively by transcranial Doppler (TCD) sonography. Extracranial volume flow changes can now reliably be measured with color duplex M-mode systems. The authors tested the volumetric effects of acetazolamide in patients with high-grade unilateral carotid disease to quantify the amount of flow changes. Patients in group 1 had a high-grade > 70% internal carotid artery (ICA) stenosis, without collateral flow through the ophthalmic artery (OA). Patients with occluded ICA were included in group 2 (patent OA collateralization) or group 3 (no OA collateralization) (n = 6 per group). In group 1, common carotid artery (CCA) volume flow in the stenotic (normal contralateral) side increased from 271 (388) ml/min by 52 (54%) with 1 g aceta-zolamide intravenously. Simultaneously, middle cerebral artery (MCA) flow velocities increased from 54 (56) cm/s by 47 (53%). In group 2, extracranial volume flow increased from 166 (444) ml/min by 19 (52)%. MCA flow velocities increased from 43 (65) cm/s by 13 (30)%. In group 3, volume flow increased from 159 (467) ml/min by 2 (46)%. Intracranial flow velocities rose from 49 (54) cm/s by 27 (41)%. Volume flow data showed the expected decline in patients with high-grade ICA stenosis and even more pronounced in patients with occlusion of the vessel. Cerebral reserve capacity was less sufficient in patients with a patent OA, despite an additional supply of 30 ml/min, indicating a hemodynamically critical situation.

Five disaccharides related in structure to the glycans of vertebrate mucins have been chemically synthesized using orthogonal blocking, coupling and deblocking techniques. These include 2-naphthylmethyl 3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1 --> 4)-2-acetamido-3,6-di-O-acetyl-2-deoxy-beta-D-glucopyranoside (6), 2-naphthylmethyl 2-aceta-mido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1 --> 3)-2,4,6-tri-O-acetyl-beta-D-galactopyranoside (14), 2-naph-thylmethyl2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl-(1 --> 3)-2-acetamido-4,6-di- O-acetyl-2-deoxy-alpha-D-galactopyranoside (20), 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1 --> 3)-2-acetamido-4,6-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside (23) and 2-naphthylmethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glu-copyranosyl-(1 --> 6)-2-acetamido-3,4-di-O-acetyl-2-deoxy-alpha-D-galactopyranoside (27). These per-O-acetylated compounds were fed to U-937 cells to test their ability to prime oligosaccharide synthesis, inhibit glycoprotein biosynthesis and alter adhesion to E-selectin expressed on endothelial cells. The results show that 6, 14, and 20 served as substrates for oligosaccharide synthesis. The generation of glycoside-primed glycans altered the formation of glycoproteins on the cell surface and inhibited cell adhesion dependent on E-selectin.

The role of angiogenesis inhibition in the antitumor activity of recombinant murine interleukin 12 (rmIL-12) was studied in K1735 murine melanomas, the growth of which is rapidly and markedly suppressed by rmIL-12 treatment. On the basis of the prediction that tumor ischemia should result from therapeutic angiogenesis inhibition, tumor cell hypoxia was evaluated as a marker of ischemia using the EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)aceta mide] approach. This method measures intracellular binding of the nitroimidazole EF5, which covalently binds to cellular macromolecules selectively under hypoxic conditions. Whereas 1 week of rmIL-12 treatment effectively inhibited K1735 cell-induced angiogenesis in Matrigel neovascularization assays, 2 weeks of treatment were needed before severe tumor cell hypoxia was detected in K1735 tumors. The hypoxia that developed was regional and localized to tumor areas distant from blood vessels. The great majority of severely hypoxic tumor cells were apoptotic, and in vitro studies indicated that the degree of hypoxia present within treated tumors was sufficient to trigger K1735 apoptosis. Tumor cell apoptosis was also prevalent in the first week of rmIL-12 treatment when few cells were hypoxic. In vitro studies indicated that this non-hypoxia-related apoptosis was induced directly by IFN-gamma produced in response to rmIL-12 administration. These studies reveal that rmIL-12 controls K1735 tumors initially by IFN-gamma-induced apoptosis and later by hypoxia-induced apoptosis. They also establish hypoxia as an expected result of tumor angiogenesis inhibition and a mediator of its therapeutic effect.

Trifluralin [2,6-dinitro-N,N-dipropyl-4-(trifluoromethyl)benzenamine], metolachlor [2-chloro-N-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) aceta mide], and metribuzin [4-amino-6-(1,1-dimethylethyl)-3-(methylthio)-1,2,4,-triazin-5(4H) -one] were selected to study adsorption and leaching potentials related to pollution on Commerce silty clay loam soil near Baton Rouge, Louisiana. At a I:10 soil/water ratio, the Koc values for trifluralin, metolachlor and metribuzin were 875, 135, and 96, respectively. Leaching of these herbicides was evaluated in soil columns (5.4 cm i.d. x 26 cm long). Total recoveries of the herbicides applied to the soil column were 73.1% +/- 4.1%. When the soil columns were leached with three pore volumes of water, the distributions of trifluralin in soil and leachate were 99.993% and 0.007% of the total recoveries, respectively. The distributions of metolachlor was 65.27% in soil and 34.7% in leachate. The distributions of metribuzin was 11.42% in soil and 88.58% in leachate. The results showed that metolachlor and metribuzin were readily leached, while trifluralin was strongly adsorbed to soil. Leaching of three herbicides in the soil column followed the leaching trends of their calculated leaching indices 1.41 x 10(4), 4.18 x 10(6), and 3.38 x 10(8) for trifluralin, metolachlor, and metribuzin, respectively. The results of the study demonstrated the potential of pollution for metolachlor and metribuzin to be leached into the ground water in soils with shallow aquifer.

We have investigated the hypoxia inducibility of vascular endothelial growth factor (VEGF) in multicellular tumor spheroids of HT29 cells using a monoclonal antibody to a fluorinated bioreductive drug, EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)aceta mide], a chemical probe for hypoxia. We have shown that VEGF expression is predominantly localized in interior spheroid cells that are sufficiently hypoxic to bioreductively activate the 2-nitroimidazole and produce immunologically detectable adducts of the EF5 compound. Northern blotting analyses demonstrated that VEGF165 is the predominant form of VEGF produced by HT29 cells and that the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate did not induce VEGF expression. This study demonstrates that VEGF expression is up-regulated in response to hypoxia and in the microenvironments found in human multicellular tumor spheroids. This investigation also illustrates the utility of the EF5 binding in multi-cellular tumor spheroids as a means of studying the expression and regulation of hypoxia-inducible genes.

The authors present their five-year experience with triple osteotomy of the pelvis, as described by Steele, in a group of 31 patients and 35 operated hip joints. The mean age of the patients was 20 years, the mean follow up period 28 months (4 - 55). Prerequisites of surgery according to the authors are: 1. congruence of the head of the femur and aceta bulum, spherical or aspherical, before operation; 2. the possibility to achieve spherical or aspherical congruence by surgery; 3. sufficient functional range of movements in the hip joint, in particular inner rotation. The subjective satisfaction of patients with surgery was 79%, objective evaluation according to Harris revealed slight improvement on average from 64 to 76 points from a total of 91 attainable points. The operation does not significantly restrict movement in the hip joint. The mean gain of Sharp's angle was 15 , Wiberg's angle 23 and the AHI index 24%. As to complications, in 60% a pseudoarthrosis of the lower arm of the ischium developed with no impact on subjective or clinical results; a deep infection in one patient led to poor results as a result of severe insufficiency of the pelvifemoral muscles; discission of the femoral vein was treated at operation by suture without serious sequelae. The subjective and clinical results can be adversely influenced by the development of insufficieny of the pelvifemoral muscles due to incorrect reinsection to the blade of the ilium. Triple osteotomy of the pelvis should be performed only by experienced surgeons. However, if the technique is mastered it offers a very good opportunity to resolve insufficiency of the tectum of the head of the femur, possibly in combination with operations of the fe-mur/varisation osteotomy or distalisation of the greater trochanter in a single stage or valgisation distraction osteotomy in two stages. Key words: triple osteotomy of the pelvis according to Steel, osteotomy of the proximal femur.

The trisaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->6)-O-2-aceta mid o-2-deoxy- beta-D-glucopyranosyl-(1-->6)-2-acetamido-2-deoxy-alpha- and -beta-D-glucopyranoside (16a and 16b), the tetrasaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->4)-O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->6)-O-2-aceta mid o-2-deoxy- beta-D-glucopyranosyl-(1-->6)-2-acetamido-2-deoxy-alpha- and -beta-D-glucopyranoside (19a and 19b), and the pentasaccharides allyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->8)-O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->4)-O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2-->6)-O-2-aceta mid o-2-deoxy-bet a -D-glucopyranosyl-(1-->6)-2-acetamido-2-deoxy-alpha- and -beta-D-glucopyranoside (23a and 23b) were prepared. The glycosidic linkages were formed using 1,3,4,6-tetra-O-acetyl-2-chloroacetamido-2-deoxy-beta-D-glucopy ran ose (6) and FeCl3 as promoter as well as per-O-acetylated Kdo mono- and di-saccharide bromide derivatives (12 and 20) under Helferich conditions. The oligosaccharides, which correspond to dephosphorylated part-structures of enterobacterial and chlamydial lipopolysaccharides, were characterized by NMR spectroscopy as well as plasma desorption and matrix-assisted laser desorption mass spectrometry.

The efficacy of p.o. semisynthetic glycolipid LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-aceta mide-4-trans- octadecene) treatment in stroke was studied in a permanent left middle cerebral artery occlusion model in the rat. A dose-dependent increase of plasma LIGA20 and its presence in the brain were documented after p.o. drug application. Oral administration of 50 to 200 mg/kg of LIGA20, initiated 24 hr before middle cerebral artery occlusion and continued for 7 days, reduced the motor and cognitive impairment after the stroke, measured by the rotarod and the passive avoidance test, respectively. The 10-mg/kg dose was effective when given i.v. but not p.o. Oral treatment with 100 mg/kg of LIGA20 reduced the infarct size in the cortex but not in the ischemic core (the striatum). No biochemical or behavioral adverse effects of LIGA20 treatment were observed. Further studies are needed to evaluate the full therapeutic potential of this compound.