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Temperature control and solvent specification are used to reduce aromatic aldehydes and ketones to intermediate alcohols rather than methylene derivatives using HCO2NH4 as a catalytic hydrogen transfer agent. A mechanism for the catalytic reduction is proposed.

Forecasting diarrheagenic E. coli contamination of aquatic resources to prevent outbreaks largely depends on rapid and accurate diagnostic testing in a few hours. Real-time PCR is widely used for quick culture-free quantitative enumeration of pathogenic bacteria in environmental samples. In this study, real-time PCR in molecular beacon format was used for detection and culture-free quantitative enumeration of enterotoxigenic Escherichia coli (ETEC) harboring LT1 gene in a sewage-impacted south Asian Gangetic riverine system. The quantitative budget for ETEC in surface water was observed to vary significantly (DMRT, p0.05) among the sites. Aquatic flora (Eichhornia crassipes, Potamogeton crispus, Potamogeton pectinatus, Ranunculus sceleratus, Polygonum glabrum, Pontederia cordata, Najas indica and strands of Spirogyra spp.) collected between sites 1 and 9 exhibited significant high levels of ETEC in comparison to their representatives collected from pristine area. The level of ETEC harboring LT1 gene observed in leafy vegetables cultivated along the banks was in the following order: mint leavescorianderspinachmethi leaves. The study suggests that the aquatic flora and cultivated leafy vegetables in the south Asian Gangetic riverine system are environmental reservoirs for enterotoxigenic Escherichia coli.

The preparation of a new class of isothiocyanatopeptide bifunctional chelating agents, Boc-glycyl-L-(p-NCS)phenylalanylglycylglycine ethyl ester 1, N-(S-acetylmercaptoacetyl)-L-(p-NCS)phenylalanyl-glycylglycine ethyl ester 2, and N-(S-acetylmercaptoacetyl)glycyl-L-(p-NCS)phenylalanylglycine ethyl ester 3, starting from Boc-L-(p-nitro)phenylalanine 5 is described. The key intermediates, nitropeptides 7, 8 and 12, were prepared by standard DCC coupling and a deprotection procedure. The nitropeptides 7 and 12 on condensation with N-succinimidyl-S-acetylthioacetate provided a good yield of the corresponding S-(acetylmercaptoacetyl) nitropeptides 10 and 13, respectively. Catalytic hydrogenolysis of compounds 8, 10 and 13, followed by thiophosgenyation gave 28-95% yield of target products 1, 2 and 3, respectively. Compounds 1-3 were conjugated to the monoclonal antibody D612 reactive with human colon carcinoma using 12/1 to 60/1 ligand to antibody molar ratios, and the conjugates were labeled with 99mTc. The in vitro cell binding results of these immunoconjugates demonstrate that they retained their antibody binding specificity. © Munksgaard 1996.

Shiga toxin-producing Escherichia coli (STEC) causes worldwide outbreaks of food and waterborne diseases. Rapid identification of causative agents is critical for early intervention in the case of widespread diarrheal epidemics to prevent mortality. In this study, a Molecular-Beacon targeting stx2 gene (highly associated with human illness) was designed to develop a culture-independent real-time PCR assay for detection and quantification of STEC in water samples. The assay could detect lowest 10 genomic equivalent (GE) of the reference strain (E. coli I.T.R.C.-18) per PCR or 100 GE/mL. The presence of 106 CFU/mL of non-pathogenic E. coli DH5α has no impact on sensitivity of the assay. The assay could successfully enumerate STEC in surface water (collected from a sewage impacted river) and potable water samples collected from Lucknow city without prior enrichment. The assay will be useful in pre-emptive monitoring of surface/potable waters to prevent waterborne outbreaks caused by STEC.

Temperature control and solvent specification are used to reduce aromatic aldehydes and ketones to intermediate alcohols rather than methylene derivatives using HCO2NH4 as a catalytic hydrogen transfer agent. A mechanism for the catalytic reduction is proposed.

The catalytic reduction of a variety of α, β-unsaturated compounds into saturated analogs in the presence of other reducible moieties is described using ammonium formate as a hydrogen source. The rate dependence on the concentration of Pd-C catalyst as well as on 5% Pd-BaSO4 and Ra-Ni are also characterized.

Low numbers (15-100CFU) of Salmonella in food or water may pose a public health risk. The management of infections caused by Salmonella spp. during outbreaks or forecasting of contamination of aquatic resources largely depends on rapid, sensitive and accurate diagnostic in few hours. In this study, a real-time PCR assay in Molecular-Beacon format was developed and culture-independent quantitative enumeration of Salmonella spp. in surface and potable water is being reported for the first time from northern part of India. Molecular Beacon was designed in highly conserved region of invA gene (present in wide range of Salmonella serotypes including all subspecies) encoding an essential component of the invasion associated specialized type O protein secretion apparatus for detection of Salmonella spp. in water. The assay could detect directly 10 and 1 genomic equivalent of Salmonella typhimurium ATCC 14028 per PCR with detection probability of 100 and 20%, respectively. Further, the assay could detect 10CFU/PCR or more of reference strain (S. typhimurium ATCC 14028) without any enrichment in the presence of 10(8)CFUml(-1) of non-pathogenic E. coli (E. coli DH5alpha) with 100% detection probability. The assay could enumerate Salmonella spp. in surface (n=40) and potable waters (n=10) directly (without enrichment). Results indicate that northern India is at high risk of developing Salmonella borne infections. Further, real-time PCR assay in Molecular Beacon format can be used for identification of critical contamination points in natural water resources and potable water distribution systems, necessary to implement vaccination plan timely for prevention of waterborne outbreaks caused by Salmonella spp.

Enterococci serve as an "indicator" of fecal contamination for recreational water quality. The vancomycin-resistant-enterococci (VRE) are emerging environmental contaminants in the surface waters. The aim ofthis study wasto develop a rapid and specific molecular beacon probe (MBP)-based real-time PCR assay for detection of vanA gene in surface waters and aquatic macrophyte. The limit of detection (LOD) of the MBP assay was 1 CFU/mL of VRE [r = 0.943; PCR efficiency = 99.7%] in 2-fold dilution format within 2.5 h and demonstrated high specificityfor environmental enterococci isolates exhibiting VanA phenotype (n=25). VRE were detected from downstream surface waters of the rivers impacted by point sources of pollution and recreational activities.The probe detected vanA gene in rootmat associated microbiota of E. crassipes (Mart) Solms. an aquatic nuisance weed, at eutrophic sites of the surface waters (ANOVA p0.001). In addition, the assay enabled detection of otherwise nondetectable vanA gene concentration in the upstream sites of two Indian rivers (Student's ttest p0.001). The MBP assay developed can be used for sensitive and rapid detection of VRE in surface waters and identification of nonpoint sources of pollution for implementation of preventive measures to protect human health.

Rapid diagnostics and risk assessment of the pathogens is possible by Real-Time Polymerase Chain Reaction (PCR) probes like TaqMan, Molecular Beacon (MB) and FRET. However, validation of such probes for real-life samples is an expensive and time consuming proposition. Hence, development and comparison of real-time probes in silico can be the first step in selection of most appropriate probe chemistry. The virulence genes specific for a model pathogen, Escherichia coli O157:H7, transmitted worldwide by contaminated water and food, were chosen to compare probe chemistries. MB was observed to be the best probe chemistry for virulence genes stx1, stx2 and eae, while FRET was preferred for hlyA gene, based on Tm and free energy values for self-dimer, hairpin and cross-dimer. Secondary structure analysis indicated that MB design was flexible and less dependent on nucleotide arrangement and repetitive sequences in the genes compared to TaqMan and FRET probes. In addition, multiplexed MB probes could be a feasible option using a single non-fluorescent quencher for high throughput diagnostics.

Aims: To determine the occurrence of Escherichia coli harbouring virulence markers of shiga- or entero-toxins and resistance to antimicrobials in surface waters. Methods and Results: Surface water samples were collected at six locations of the river Gomti. E. coli isolates (n = 90) were characterized for their pathogenic potential using polymerase chain reaction to detect virulence genes as well as their sensitivity to antimicrobial agents using disc diffusion methods. In this study, 57·8% of E. coli isolates exhibited resistance to three or more antimicrobial agents. Sensitivity to cephotaxime, gentamicin and norfloxacin was observed in 7·8%, 48·9% and 77·8% of isolates, respectively. Both stx1 and stx2 genes were present in 15·6% of isolates while remaining isolates had either stx1 (17·8%) or stx2 (6·7%). The stx1 gene (33·3%) was more prevalent than stx2 (22·2%). The results indicate that the LT1 and ST1 genes were positive in 21·2% of isolates. Conclusions: The presence of multi-drug resistance and virulence genes in E. coli isolated from surface water being used for domestic and recreational purposes may result in waterborne outbreaks. Significance and Impact of the Study: The data will be useful in monitoring surface waters for forecasting and management of waterborne outbreaks.

A procedure for labeling the novel serotonin uptake inhibitor, citalopram [1-(3-(dimethylamino) propyl-1-(p-fluorophenyl)-5-phthalancarbonitrile, Lu 10-171], with the positron emitting radionuclide11C (t 1 2 = 20.4 min ) has been developed, in order to permit the pharmacokinetics of this compound to be studied in man. The procedure involves the reaction of [11C]iodomethane with desmethylcitalopram in acetone in the presence of sodium hydroxide base at 65° for 8–10 min; this was followed by purification by a column which contained, in series silica gel and basic alumina, and produces no carrier added [11C]citalopram in radiochemical yield (18–66% at EOB) and radiochemical purity (> 95%). The specific activity of [11C]citalopram was 2.52 × 103–16.06 × 103GBq/mmol (68–434 Ci/mmol) at the end of synthesis.

The consumption of polluted surface water for domestic and recreational purposes by large populations in developing nations is a major cause of diarrheal disease related mortality. The river Ganga and its tributaries meet 40% of the water requirement for drinking and irrigation in India. In this study, Escherichia coli isolates (n=75) of the river Ganga water were investigated for resistance to antimicrobial agents (n=15) and virulence genes specific to shiga toxin (STEC) and enterotoxin producing E. coli (ETEC). E. coli isolates from the river Ganga water exhibit resistance to multiple antimicrobial agents. The distribution of antimicrobial agent resistance in E. colivaries significantly (chi2: 81.28 at df = 24, p0.001) between the sites. Both stx1 and stx2 genes were present in 82.3% of STEC (n=17) while remaining isolates possess either stxl (11.8%) or stx2 (5.9%). The presence of eaeA, hlyA, and chuA genes was observed in 70.6, 88.2, and 58.8% of STEC, respectively. Both LT1 and ST1 genes were positive in 66.7% of ETEC (n=15) while 33.3% of isolates harbor only LT1 gene. The prevalence of multi-antimicrobial-agent resistant E. coli in the river Ganga water poses increased risk of infections in the human population.

Diarrheagenic E. coli strains contribute to water related diseases in urban and rural environment in developing and developed world. E. coli pathotype and pathogenicity varies due to complex multifactorial mechanism involving a large number of virulence factors. Rapid assessment of the virulence pattern of E. coli isolates is possible by Real-Time PCR probes like TaqMan. For designing TaqMan probes and primers for multiplex PCR selected E. coli gene sequences: stx1, stx2, hlyA, chuA, eae, lacZ, lamB and fimA were retrieved from NCBI's GenBank database. The alignment of the multiple sequences and analysis of conserved sequences was carried out using ClustalW and BLAST programs. The primers and Taqmen probes were designed using Beacon Designer software version 2.1 for two multiplexed PCR assays. In silico PCR simulation of these assays showed PCR products for stx2 (248bp) stx1 (102 bp), lacZ (228bp) and lamB (86 bp) in multiplex #1 and eae (200bp), chuA (147 bp), hlyA (141bp) and fimA (79 bp) in multiplex #2, respectively. These multiplexed PCR amplification products and probes can be used to identify and confirm presence of O157:H7/ H7-, O157:H43/45 and O26:H-/H11 serotypes. In conclusion, multiplex Real-Time Polymerase Chain Reaction oligomers and TaqMan probes designed and validated in silico will be helpful in management of water quality and outbreaks, by improving specificity and minimizing time needed for in vitro verification work.

A series of novel 4-(N-acyl)-2,3-dihydro-1H-isoindol-1-ones have been prepared from methyl-3-nitro-2-methylbenzoate and linked through various spacers to the adenosine derivatives 11 and 12. We found that potent inhibition of poly(ADP-ribose)polymerase-1 (PARP-1) was achieved when isoindolinone was linked to adenosine by a spacer group of a specific length. Introduction of piperazine and succinyl linkers between the isoindolinone and adenosine core structures resulted in highly potent compounds 8a and 10b, which showed IC(50) values of 45 and 100 nM, respectively.

Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase.

To ensure the desired impact of the extension programmes, it is imperative that suitable extension strategies are evolved to disseminate different technologies to different categories of the farmers. The study was conducted in five villages of Tarapur Block of Munger District of Bihar, India. The villages were denoted by V1, V2, V3, V4 and V5 of a given district and as many as 30 farmers, 10 each from marginal, small and large farmers categories called groups, were selected from each village randomly and were represented by G1, G2 and G3 of a given village, respectively. The 30 farmers forming the experiment group in the villages were trained to seek the information/message and were closely monitored while under exposure through e-extension. On the other hand, under e-based Management of Agricultural Technology (e-MAT) treatment, the group was exposed to the technology packages through e-extension well mixed with all the three extension methods. Lectures, visit, pamphlets, charts, banners, specimens, etc., which were commonly used with the first three methods were also used with all the five methods in this experiment for consecutive two years. As a result, it was seen that e-MAT is an effective extension method. There were significant differences in the mean knowledge scores, attitude scores and adoption quotient of trained and untrained farmers about the package of practices of high-yielding varieties of wheat and rice. The trained farmers had significantly higher knowledge scores, attitude scores and adoption quotient about the package of practices of high-yielding varieties of wheat and rice than untrained farmers.

A new bifunctional chelating agent MAGIPG was synthesized in good yield using Boc-p-nitro-phenylalanine as the starting material. 99mTc-labeled-MAGIPG-D612 conjugates reactive with human colon cancer were prepared in 3% to 15% yield with a radiochemical purity of 63% to 97%. 186Re-labeled MAGIPG-D612 conjugates were prepared with a 7% to 30% yield and a radiochemical purity of 82% to 98%. The biodistribution results demonstrate that these radioimmuno-conjugates selectively localized in LS174T human colon cancer xenografts.

TPS2627 Background: Thioureidobutyronitrile, kevetrin, has demonstrated anti-tumor activity in several wild type and mutant p53 human tumor xenografts without evidence of genotoxicity. In wild type p53 models, kevetrin induces cell cycle arrest and apoptosis through activation and stabilization of wild type p53, resulting in increased expression of p53 target genes p21 and PUMA. Kevetrin also alters processivity of MDM2, and induces monoubiquitination of wild type p53, enhancing its stability (AACR 2011 abstract 4470). Mutant p53 is a complex target since it is an array of mutant proteins with oncogenic properties. Kevetrin induces degradation of oncogenic mutant p53 and induces apoptosis (AACR 2012 abstract 2874). Kevetrin therefore has the unique ability to target both wild type and mutant p53 tumors thereby controlling tumor growth in a wide range of preclinical tumor models. Methods: Adults with refractory locally advanced or metastatic solid tumors, acceptable liver and kidney function, and hematological status were eligible. Objectives include determination of DLT, MTD, recommended phase 2 dose, pharmacokinetics (PK), pharmacodynamics (PD), and evaluating preliminary evidence of antitumor activity. Kevetrin is given as a 1-hour intravenous infusion once weekly for 3 weeks in 28-day cycles. The starting dose was 10 mg/m2. In a 3+3 design, groups of 3-6 patients are evaluated for toxicity at each dose level. Dose escalation is based upon the number and intensity of adverse events in cycle 1. Kevetrin PK is characterized for the first and last doses given in cycle 1. Kevetrin induced expression of p21 in lymphocytes in preclinical studies; therefore p21 expression in peripheral blood mononuclear cells will be measured as a PD biomarker. Antitumor activity by RECIST 1.1 criteria and serum tumor markers will be assessed. The p53 status of tumors of selected patients will be determined. The second cohort is currently under evaluation. Conclusion: In preclinical models, Kevetrin has activity against tumors harboring both wild type and mutant p53 by diverse mechanisms. A first-in-human dose escalation trial is underway. Clinical trial information: NCT01664000.

Our studies showed that Kevetrin™, a small molecule currently under development, has potent antitumor activity in several wild type and mutant p53 human tumor xenografts e.g. A549, PC-3, MDA-MB-231, HT-29, NCI-H1975, HCT-15, K-562, LNCaP. To investigate the mechanism of action of its antitumor activity in different xenograft models, we assessed Kevetrin's effects on apoptosis and cell cycle progression. Rb-E2F and MDM2-p53 pathways are crucial regulators of cell cycle progression. Remarkably, both Rb-E2F and MDM2-p53 pathways are defective in most, if not all, human tumors. There is extensive crosstalk between the Rb-E2F and MDM2-p53 pathways, especially between the transcription factors E2F1 and p53, which influence vital cellular decisions. In wild type p53 human lung carcinoma (A549), Kevetrin showed a concentration dependent increase in activation of p53 by Western blot analysis. Activated p53 triggered apoptosis by inducing the expression of PUMA. Kevetrin also increased the expression of the target gene p21, an inhibitor of cell cycle progression. Kevetrin induced apoptosis in a transcriptional independent way by altering the E3 ligase processivity of MDM2. Kevetrin strongly induced apoptosis in multiple tumor cell lines characterized by activation of caspase3 and PARP. E2F1 is a pivotal transcription factor that integrates signals from a variety of G1/S phase regulators and modulates diverse functions, such as DNA synthesis, mitosis, apoptosis and senescence. E2F1 overexpression, observed in most tumors, is associated with tumor growth. Cells which overexpress E2F1 proved to be immune to induction of senescence. A recent study showed that depletion of E2F1 hinders cell cycle progression and induces senescence. Kevetrin down regulated E2F1 expression in various p53 wild type and mutant cell lines. Kevetrin also down regulated the E2F1 target gene thymidylate synthase (TS) in various tumor cell lines. Several reports have shown E2F1 overexpression correlates with TS expression. Effective inhibition of TS by Kevetrin could play a crucial role in tackling the problem of resistance. Kevetrin acting through both major pathways of tumor suppression, Rb-E2F and MDM2-p53, has far reaching consequences. Due to the complexity of proapoptotic and antiapoptotic pathways with multiple players involved and redundant signaling networks, blocking only one antiapoptotic factor may not result in robust antitumor activity. However, Kevetrin acts via multiple targets to produce potent efficacy in various xenograft tumor models. We have also demonstrated that Kevetrin is non-genotoxic. DNA damaging drugs result in rapid phosphorylation of H2A.X at Ser 139 by PI3K-like kinases; however, Kevetrin did not induce phosphorylation of H2A.X. Since Kevetrin was well-tolerated in GLP safety pharmacology and toxicity studies, we have submitted an IND application for a Phase I clinical trial at Dana Farber / Harvard Cancer Center for 2012. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2874. doi:1538-7445.AM2012-2874

We have previously shown that Kevetrin, a small molecule currently under development, has potent antitumor activity in human multi-drug resistant carcinoma xenograft models while being well tolerated. To investigate the mechanism of action for its potent antitumor activity, we assessed Kevetrin's effect on apoptosis, cell cycle progression, including underlying molecular mechanisms. Here we report that Kevetrin strongly induced cell cycle arrest and apoptosis in a human lung adenocarcinoma cell line (A549) using the TUNEL assay and FACS analysis; similar results were observed using a human breast carcinoma cell line (MDA-MB-231). Treatment of A549 cells with 400 µM of Kevetrin for 48 hours resulted in G2/M phase cell cycle arrest that was associated with a marked decline in levels of G2/M regulatory proteins, including CDK1 and cdc25B, and increased expression of Wee1. Further, Kevetrin-mediated growth inhibition of A549 correlated with apoptosis induction that was characterized by cleavage of procaspase-3 and poly (ADP-ribose) polymerase (PARP). The p53 tumor suppressor is a well characterized transcription factor controlling cell growth and apoptosis during times of cellular stress. The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. In cancer development, the resistance of cells to apoptosis is one of the crucial steps. The reactivation of p53 in tumor cells should trigger massive apoptosis and eliminate the tumor. Interestingly, Kevetrin treatment caused enhanced activated p53 levels in A549 cells. Activation of p53 can lead to cell cycle arrest and apoptosis. Western blotting revealed a concentration dependent increase in phosphorylation of p53 at serine 15. The phosphorylation of p53 at serine 15 leads to reduced interaction between p53 and its negative regulator, the oncoprotein MDM2. We also found that Kevetrin increased expression of p53 target genes such as p21 (Waf1). The tumor suppressor protein p21 (Waf1) acts as inhibitor of cell cycle progression. Finally, we also found that p53 induced apoptosis by inducing the expression of PUMA. Our study shows that Kevetrin activates p53 functions in tumor cells. Thus Kevetrin is a strong candidate as an anticancer drug that targets p53. Based on our studies we plan to initiate a Phase I clinical trial in 2011. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4470. doi:10.1158/1538-7445.AM2011-4470

The Chernobyl nuclear reactor accident in Russia in 1986 has further revealed the susceptibility of the environment to radioactive contamination. This can have serious implications for the safety of milk as well as other foods. Global fallout and other isotope releases can threaten to increase the radionuclide levels in milk alarmingly, and thus make it unfit for human consumption. Perception of such fears in the past resulted in considerable research efforts being directed towards radioactive decontamination of milk by different means. The holding of milk and milk products long enough to deactivate certain radioisotopes prior to consumption, conversion of milk into butter, and manufacturing cheese by using modified processes are some of the approaches in minimizing the radioactivity risk to consumers. Extensive studies carried out in the USA have shown that though somewhat expensive, ion-exchange treatment of milk in large-scale, automated plants can eliminate 90% or more of the radionuclides of concern, i.e. strontium-90, and iodine-131, and much of caesium-137. Various factors affecting the efficiency of the ion exchange process and properties of the treated milk are reviewed. Other processing techniques such as electrodialysis are also briefly discussed in relation to removal of radionuclides from milk.

A new radioiodination reagent, 3-iodophenylisothiocyanate (3-IPI) has been developed for coupling to monoclonal antibodies. The starting material, 3-tri-n-butylstannylphenylisothiocyanate was prepared via a reaction of hexabutylditin with 3-bromoaniline, followed by treatment with thiophosgene with an overall yield of 72%. The radioiodination of this tin precursor with Na[125I]I/iodogen in chloroform gave 3-[125I]IPI in 23-55% radiochemical yield and 81-99.6% radiochemical purity. Purification of the impure product by high pressure liquid chromatography increased the radiochemical purity of the product up to 99%. These results suggest that 3-IPI may be a useful ligand for radioiodination and coupling to a variety of monoclonal antibodies.

A series of methyl and ethyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates (7-19) and methyl 5-carbamoyl-1H-benzimidazole-2-carbamates (24-34) have been synthesized via the reaction of an appropriate alcohol or amine with the acid chloride derivatives 6a or 6b at room temperature. Reaction of an alcohol with acid chloride 6a at reflux temperature afforded transesterified products 20-23 in good yield. Treatment of methyl 5-amino-1H-benzimidazole-2-carbamate with substituted benzoyl chlorides furnished the methyl 5-benzamido-1H-benzimidazole-2-carbamates (36-38). Compounds 9, 16, 20, and 22 demonstrated significant growth inhibition in L1210 cells with IC50's less than 1 microM. Growth inhibition by this series of compounds appears to be associated with mitotic spindle poisoning. All the compounds tested, 9, 10, 19, 20, 22, and 23, caused significant accumulation of L1210 cells in mitosis. Compounds 7, 9, 19, 25, 26, 27, and 36 showed significant in vivo antifilarial activity against adult worms of Brugia pahangi, Litomosoides carinii, and Acanthocheilonema viteae in experimentally infected jirds.

BackgroundSurface waters quality has declined in developing countries due to rapid industrialization and population growth. The microbiological quality of river Ganga, a life-sustaining surface water resource for large population of northern India, is adversely affected by several point and non-point sources of pollution. Further, untreated surface waters are consumed for drinking and various household tasks in India making the public vulnerable to water-borne diseases and outbreaks. Enterococci, the 'indicator' of water quality, correlates best with the incidence of gastrointestinal diseases as well as prevalence of other pathogenic microorganisms. Therefore, this study aims to determine the distribution of species diversity, dissemination of antimicrobial-resistance and virulence-markers in enterococci with respect to rural-urban landscape along river Ganga in northern India.ResultsEnterococci density (χ2: 1900,df: 1;p< 0.0001) increased from up-to-down gradient sites in the landscape. Species diversity exhibit significant (χ2: 100.4,df: 20;p< 0.0001) and progressive distribution ofE. faecalis,E. faecium,E. duransandE. hiraedown the gradient. Statistically discernible (p: 0.0156 – < 0.0001) background pool of resistance and virulence was observed among differentEnterococcusspp. recovered from five sites in the up-to-down gradient landscape. A significant correlation was observed in the distribution of multiple-antimicrobial-resistance (viz., erythromycin-rifampicin-gentamicin-methicillin and vancomycin-gentamicin-streptomycin;rs: 0.9747;p: 0.0083) and multiple-virulence-markers (viz.,gelE+esp+;rs: 0.9747;p: 0.0083;gelE+efaA+;rs: 0.8944;p: 0.0417) among differentEnterococcusspp.ConclusionOur observations show prevalence of multiple-antimicrobial-resistance as well as multiple-virulence traits among differentEnterococcusspp. The observed high background pool of resistance and virulence in enterococci in river waters of populous countries has the potential to disseminate more alarming antimicrobial-resistant pathogenic bacteria of same or other lineage in the environment. Therefore, the presence of elevated levels of virulent enterococci with emerging vancomycin resistance in surface waters poses serious health risk in developing countries like India.

Positron Emission Tomography (PET) is a powerful imaging diagnostic tool which uniquely provides qualitative and quantitative measurement of metabolic processes in vivo in normal and pathological tissue via application of appropriate radiotracers. Recently, there has been great interest in the development of fast and efficient new synthetic methodologies for positron emitting radiolabeled pharmaceuticals which can be used as tracers for P.E.T. studies. In the last decade, a variety of N-[11C] labeled radiopharmaceuticals1–2 have been synthesized via methylation of the appropriate desmethyl precursors with [11C]CH3I or reductive methylation with [11C]HCHO/NaBH3CN. In principle, both of these reagents [11C]CH3I or [11C]HCHO have been prepared from the more readily available [11C]CO2 via reduction to [11C]CH3OH, followed by iodination or oxidation as illustrated in Scheme-1. Further examination of the N-[11C] radiopharmaceuticals reveals that these bioactive molecules can be easily prepared directly from [11C] carbon dioxide under appropriate conditions. We have, therefore, investigated the use of [11C]CO2 as a radiolabeled precursor in the preparation of a variety of [11C] labeled compounds. In order to develop new synthetic methodologies for direct incorporation of [11C]CO2 into bioactive molecules, synthesis should be short and efficient and should be complete within three half-lives of the radioisotope. In general, literature synthetic procedures3 using [12C] or [14C]CO2 are not applicable for the synthesis of [11C] labeled radiopharmaceuticals because of the short 20.4 min half-life of the [11C] isotope. Hence, either extremely modified or entirely new procedures are desirable. A general reaction of [11C]CO2 with organometallics has been widely used for the preparation of [11C] carboxylic acid derivatives.

Reductive carboxylation of a variety of secondary and primary amines to the corresponding N-methylated amines in the presence of various functional groups such as chlorosubstituents, carbon-carbon double bonds and phenolic hydroxyls is described.

Several 5-benzoyl-2-thiobenzimidazole and 2-thiobenzimidazole aliphatic acids, esters, and N,N-dialkyl-carboxamides and thiocarboxamides were prepared by reacting bromo aliphatic acids, bromo aliphatic esters, and N,N-dialkylcarbamoyl or thiocarbamoyl chlorides with 5-benzoyl-2-thiobenzimidazole or 2-thiobenzimidazole in the presence of base. 2-Thiocarbomethoxy- and 2-thiocarboethoxybenzimidazole were prepared by the reaction of 2-thiobenzimidazole with methyl or ethyl chloroformate in the presence of base. However, the reaction of 5-benzoyl-2-thiobenzimidazole with ethyl chloroformate, afforded 5-benzoyl-2-ethylthiobenz-imidazole.

A one-pot synthesis of [11C] labeled tamoxifen has been developed via reductive carboxylation. In this approach, [11C]CO2 is reacted with the N-trimethylsilyl derivative of desmethyltamoxifen, followed by in situ sodium bis (2-methoxyethoxy)aluminum hydride reduction, to afford impure [11C] labeled tamoxifen, which, on purification over a basic alumina-silica gel column, provided pure [11C] tamoxifen in excellent radiochemical yield (65% to 84%) and radiochemical purity (>99%). The specific activity of [11C]tamoxifen was 250–400 Ci/mmol at the end of bombardment.

Absorption and emission spectroscopy in the ultraviolet and visible regions, apart from being the earliest physical techniques of analysis, have great utility in solving a variety of structural and analytical problems [l-41. However, in many cases the quantitative determination of individual components in a mixture by UV-VIS spectroscopy becomes very difficult owing to the spectral similarities and overlapping of weak absorption bands of one component by strong absorption bands of other components. It was recently recognized that derivative spectrophotometry, introduced about three decades ago [5-81 and originally proposed by Rutherford [9], can be a very useful analytical tool for characterizing an analyte band that is overlapped by other absorption bands with different halfwidths. On differentiation, the intensity of the absorption band with a small halfwidth increases more than that of a band with a large halfwidth [10]. The central idea behind the development of the science of derivatized spe...

Various aliphatic and aromatic nitro compounds were selectively and rapidly reduced to their corresponding amino derivatives in very good yield using anhydrous ammonium formate as a catalytic hydrogen transfer agent.

Various aromatic aldehydes and ketones were reduced to the corresponding hydrocarbons using ammonium formate as the hydrogen source.

A method for deprotection of several N-benzyl derivatives of amines to the corresponding amino derivatives with ammonium formate and 10% Pd-C is reported.

A series of methyl 2-substituted purine 8-carbamates was prepared and evaluated for antifilarial activity. These purines were synthesized as aza congeners of benzimidazole carbamates which have shown significant anthelminthic activity to determine the effect that this modification might have on anthelmintic activity. The compounds were tested against the filarial infection, B. pahangi, in jirds. None of the compounds prepared in this study demonstrated antifilarial activity

A number of 2,5-disubstituted benzimidazoles have been prepared from 2-benzyl-5-nitrobenzimidazole (5) and 2-p-fluorobenzyl-5-nitrobenzimidazole (6), and evaluated as potential antifilarial agents. None of the compounds prepared in this study have demonstrated any significant antifilarial activity.

Various tertiary N-methylated amines were synthesized by using a new reductive-carboxylation approach. Secondary amines, on carboxylation with carbon dioxide under moderate reaction conditions, afforded their corresponding carbamate esters, which, on in situ lithium aluminum hydride reduction, gave desired tertiary N-methylated amines in high yield.

(1985). AN IMPROVED SYNTHESIS OF METHYL [5-BENZOYL- AND 5-p-FLUOROBENZOYLBENZIMIDAZOL-2-YL]CARBAMATES. Organic Preparations and Procedures International: Vol. 17, No. 3, pp. 215-218.

A new rapid high yield synthesis of radiolabeled N′-(4-11C-methyl)imipramine has been developed using a reductive-carboxylation approach, in which 11CO2 is reacted with either N′-trimethylsilyldesimipramine or N′-lithium derivative of desimipramine, followed by lithium aluminum hydride reduction, to give no carrier added or carrier added11C-labeled imipramine respectively. The final product is characterized by chromatographic and spectroscopic methods.

In this paper we prove that under suitable restrictions on { p n } \{ {p_n}\} and the integral modulus of continuity of a function f of Wiener’s class the Fourier series of f is summable | N , p n | |N,{p_n}| .

Reductive carboxylation of a variety of secondary and primary amines to the corresponding N-methylated amines in the presence of various functional groups such as chlorosubstituents, carbon-carbon double bonds and phenolic hydroxyls is described.

A series of 1-(5-benzoylbenzimidazol-2-yl)-3-substituted ureas have been synthesized by reacting an appropriate isocyanate with 2-amino-5-benzoylbenzimidazole or by reacting methyl (5-benzoylbenzimidazol-2-yl)carbamate with various amines. Several of the compounds have demonstrated antifilarial activity against Brugia pahangi and Litomosoides carinii.

A new synthesis is described for the production of the positron emitting radiopharmaceutical R-(+)-7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-N-[11C]methyl-1-phenyl-1H- 3-benzazepine (SCH 23390, 2a). This novel method involves reductive carboxylation, in which [11C]CO2 is reacted with the trimethylsilyl derivative of the desmethyl compound (SCH 24518, 1a) followed by treatment with lithium aluminum hydride, to afford no carrier added 11C-labeled SCH 23390. The procedure gave chemically and radiochemically pure 11C-labeled SCH 23390 in 53-72% radiochemical yield with an unoptimized specific activity of 40 Ci/mmol within 45-50 min from the end of bombardment.