opium poppy cell: Topics by Science.gov

Sample records for opium poppy cell

Thebaine in hair as a marker for chronic use of illegal opium poppy substances.

PubMed

Lee, Sooyeun; Park, Yonghoon; Han, Eunyoung; Choi, Hwakyung; Chung, Heesun; Oh, Seung Min; Chung, Kyu Hyuck

2011-01-30

Opium poppy products are often illegally used for both recreational and medicinal purposes. In order to demonstrate the ingestion of opium poppy substances, morphine, codeine and their metabolites have been identified. However, morphine and codeine also originate from the ingestion of therapeutic drugs. Therefore, thebaine, one of the main opium alkaloids, in hair was suggested as a marker for chronic use of illegal opium poppy substances in the present study. First, thebaine was included in the analyte list of our routine analytical method for the simultaneous quantification of codeine, morphine, norcodeine, normorphine and 6-acetylmorphine (6-AM) in hair, which was fully validated previously. Then, the incorporation of thebaine and other opiates into hair and the effect of hair pigmentation were examined using lean Zucker rats with both dark grey and white hair on the same body. Thebaine was also measured in hair samples from actual cases of opium poppy substance use. Consequently, thebaine in hair was demonstrated as a marker of chronic use of illegal opium poppy substances using an animal study and actual cases. Thebaine and other opiates were successfully measured in pigmented hair from rats that ingested raw opium suspension. Moreover, thebaine identified in hair excluded possibility of ingestion of pharmaceutical opiates in actual cases. Copyright Â© 2010 Elsevier Ireland Ltd. All rights reserved.
Integration of deep transcriptome and proteome analyses reveals the components of alkaloid metabolism in opium poppy cell cultures

PubMed Central

2010-01-01

Background Papaver somniferum (opium poppy) is the source for several pharmaceutical benzylisoquinoline alkaloids including morphine, the codeine and sanguinarine. In response to treatment with a fungal elicitor, the biosynthesis and accumulation of sanguinarine is induced along with other plant defense responses in opium poppy cell cultures. The transcriptional induction of alkaloid metabolism in cultured cells provides an opportunity to identify components of this process via the integration of deep transcriptome and proteome databases generated using next-generation technologies. Results A cDNA library was prepared for opium poppy cell cultures treated with a fungal elicitor for 10 h. Using 454 GS-FLX Titanium pyrosequencing, 427,369 expressed sequence tags (ESTs) with an average length of 462 bp were generated. Assembly of these sequences yielded 93,723 unigenes, of which 23,753 were assigned Gene Ontology annotations. Transcripts encoding all known sanguinarine biosynthetic enzymes were identified in the EST database, 5 of which were represented among the 50 most abundant transcripts. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) of total protein extracts from cell cultures treated with a fungal elicitor for 50 h facilitated the identification of 1,004 proteins. Proteins were fractionated by one-dimensional SDS-PAGE and digested with trypsin prior to LC-MS/MS analysis. Query of an opium poppy-specific EST database substantially enhanced peptide identification. Eight out of 10 known sanguinarine biosynthetic enzymes and many relevant primary metabolic enzymes were represented in the peptide database. Conclusions The integration of deep transcriptome and proteome analyses provides an effective platform to catalogue the components of secondary metabolism, and to identify genes encoding uncharacterized enzymes. The establishment of corresponding transcript and protein databases generated by next-generation technologies in a system with a well
Morphine biosynthesis in opium poppy involves two cell types: sieve elements and laticifers.

PubMed

Onoyovwe, Akpevwe; Hagel, Jillian M; Chen, Xue; Khan, Morgan F; Schriemer, David C; Facchini, Peter J

2013-10-01

Immunofluorescence labeling and shotgun proteomics were used to establish the cell type-specific localization of morphine biosynthesis in opium poppy (Papaver somniferum). Polyclonal antibodies for each of six enzymes involved in converting (R)-reticuline to morphine detected corresponding antigens in sieve elements of the phloem, as described previously for all upstream enzymes transforming (S)-norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole-stem and latex total protein extracts generated 2031 and 830 distinct protein families, respectively. Proteins corresponding to nine morphine biosynthetic enzymes were represented in the whole stem, whereas only four of the final five pathway enzymes were detected in the latex. Salutaridine synthase was detected in the whole stem, but not in the latex subproteome. The final three enzymes converting thebaine to morphine were among the most abundant active latex proteins despite a limited occurrence in laticifers suggested by immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine biosynthesis appears to occur only in sieve elements, whereas conversion of thebaine to morphine is predominant in adjacent laticifers, which contain morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun proteomics has substantially resolved the cellular localization of morphine biosynthesis in opium poppy.
Molecular cloning and characterization of tetrahydroprotoberberine cis-N-methyltransferase, an enzyme involved in alkaloid biosynthesis in opium poppy.

PubMed

Liscombe, David K; Facchini, Peter J

2007-05-18

S-Adenosyl-l-methionine:tetrahydroprotoberberine cis-N-methyltransferase (EC 2.1.1.122) catalyzes the conversion of (S)-stylopine to the quaternary ammonium alkaloid, (S)-cis-N-methylstylopine, as a key step in the biosynthesis of protopine and benzophenanthridine alkaloids in plants. A full-length cDNA encoding a protein exhibiting 45 and 48% amino acid identity with coclaurine N-methyltransferase from Papaver somniferum (opium poppy) and Coptis japonica, respectively, was identified in an elicitor-treated opium poppy cell culture expressed sequence tag data base. Phylogenetic analysis showed that the protein belongs to a unique clade of enzymes that includes coclaurine N-methyltransferase, the predicated translation products of the Arabidopsis thaliana genes, At4g33110 and At4g33120, and bacterial S-adenosyl-L-methionine-dependent cyclopropane fatty acid synthases. Expression of the cDNA in Escherichia coli produced a recombinant enzyme able to convert the protoberberine alkaloids stylopine, canadine, and tetrahydropalmatine to their corresponding N-methylated derivatives. However, the protoberberine alkaloids tetrahydroxyberbine and scoulerine, and simple isoquinoline, benzylisoquinoline, and pavine alkaloids were not accepted as substrates, demonstrating the strict specificity of the enzyme. The apparent K(m) values for (R,S)-stylopine and S-adenosyl-L-methionine were 0.6 and 11.5 microm, respectively. TNMT gene transcripts and enzyme activity were detected in opium poppy seedlings and all mature plant organs and were induced in cultured opium poppy cells after treatment with a fungal elicitor. The enzyme was detected in cell cultures of other members of the Papaveraceae but not in species of related plant families that do not accumulate protopine and benzophenanthridine alkaloids.
Expression Patterns Conferred by Tyrosine/Dihydroxyphenylalanine Decarboxylase Promoters from Opium Poppy Are Conserved in Transgenic Tobacco1

PubMed Central

Facchini, Peter J.; Penzes-Yost, Catherine; Samanani, Nailish; Kowalchuk, Brett

1998-01-01

Opium poppy (Papaver somniferum) contains a large family of tyrosine/dihydroxyphenylalanine decarboxylase (tydc) genes involved in the biosynthesis of benzylisoquinoline alkaloids and cell wall-bound hydroxycinnamic acid amides. Eight members from two distinct gene subfamilies have been isolated, tydc1, tydc4, tydc6, tydc8, and tydc9 in one group and tydc2, tydc3, and tydc7 in the other. The tydc8 and tydc9 genes were located 3.2 kb apart on one genomic clone, suggesting that the family is clustered. Transcripts for most tydc genes were detected only in roots. Only tydc2 and tydc7 revealed expression in both roots and shoots, and TYDC3 mRNAs were the only specific transcripts detected in seedlings. TYDC1, TYDC8, and TYDC9 mRNAs, which occurred in roots, were not detected in elicitor-treated opium poppy cultures. Expression of tydc4, which contains a premature termination codon, was not detected under any conditions. Five tydc promoters were fused to the β-glucuronidase (GUS) reporter gene in a binary vector. All constructs produced transient GUS activity in microprojectile-bombarded opium poppy and tobacco (Nicotiana tabacum) cell cultures. The organ- and tissue-specific expression pattern of tydc promoter-GUS fusions in transgenic tobacco was generally parallel to that of corresponding tydc genes in opium poppy. GUS expression was most abundant in the internal phloem of shoot organs and in the stele of roots. Select tydc promoter-GUS fusions were also wound induced in transgenic tobacco, suggesting that the basic mechanisms of developmental and inducible tydc regulation are conserved across plant species. PMID:9733527
The rules of drug taking: wine and poppy derivatives in the Ancient World. VIII. Lack of evidence of opium addiction.

PubMed

Nencini, P

1997-09-01

The widespread therapeutic use of opium and its probable ritual use is faced with the absence of any explicit description of cases of opium dependence. It is possible that this was due to a lack of diagnostic capability. However, even the attempt to uncover cases of opium dependence by systematically analyzing the literary passages in which poppies, opium, and meconium are quoted are unsuccessful. The only two cases of suspected opium addiction that can be selected in this way are those of the Emperor Marcus Aurelius and Ovid. The most parsimonious interpretation is the lack of an hedonic use of poppy derivatives, being that this kind of use is the most frequently connected with the development of addiction.
The opium poppy as a symbol of sleep in Bertel Thorvaldsen's relief of 1815.

PubMed

Tekiner, Halil; Kosar, Muberra

2016-03-01

Danish sculptor Bertel Thorvaldsen (1770-1844) is one of the most remarkable representatives of Neoclassicist sculptural art in Europe, which was largely inspired by the classical art and culture of Greek and Roman antiquity. A pair of marble reliefs, Night and Day, exhibited in the Thorvaldsen Museum (Copenhagen), marks the culmination of Thorvaldsen's relief art and is of particular interest to the history of sleep medicine. In the first relief, Night, an angel with her neck bent and eyes closed has two babies in her embrace and seems to be floating down in grief, with an owl hovering behind her. Her hair is also twined with opium poppies, the symbol of sleep and death in antiquity. Our findings suggest that this relief not only indicates a mythological association between the opium poppy and sleep but also has a strong connotation with the poppy's medicinal use for inducing sleep throughout the centuries. Copyright © 2015 Elsevier B.V. All rights reserved.
Characterization of a Flavoprotein Oxidase from Opium Poppy Catalyzing the Final Steps in Sanguinarine and Papaverine Biosynthesis*

PubMed Central

Hagel, Jillian M.; Beaudoin, Guillaume A. W.; Fossati, Elena; Ekins, Andrew; Martin, Vincent J. J.; Facchini, Peter J.

2012-01-01

Benzylisoquinoline alkaloids are a diverse class of plant specialized metabolites that includes the analgesic morphine, the antimicrobials sanguinarine and berberine, and the vasodilator papaverine. The two-electron oxidation of dihydrosanguinarine catalyzed by dihydrobenzophenanthridine oxidase (DBOX) is the final step in sanguinarine biosynthesis. The formation of the fully conjugated ring system in sanguinarine is similar to the four-electron oxidations of (S)-canadine to berberine and (S)-tetrahydropapaverine to papaverine. We report the isolation and functional characterization of an opium poppy (Papaver somniferum) cDNA encoding DBOX, a flavoprotein oxidase with homology to (S)-tetrahydroprotoberberine oxidase and the berberine bridge enzyme. A query of translated opium poppy stem transcriptome databases using berberine bridge enzyme yielded several candidate genes, including an (S)-tetrahydroprotoberberine oxidase-like sequence selected for heterologous expression in Pichia pastoris. The recombinant enzyme preferentially catalyzed the oxidation of dihydrosanguinarine to sanguinarine but also converted (RS)-tetrahydropapaverine to papaverine and several protoberberine alkaloids to oxidized forms, including (RS)-canadine to berberine. The Km values of 201 and 146 μm for dihydrosanguinarine and the protoberberine alkaloid (S)-scoulerine, respectively, suggested high concentrations of these substrates in the plant. Virus-induced gene silencing to reduce DBOX transcript levels resulted in a corresponding reduction in sanguinarine, dihydrosanguinarine, and papaverine accumulation in opium poppy roots in support of DBOX as a multifunctional oxidative enzyme in BIA metabolism. PMID:23118227
Detection of Verticillium wilt of olive trees and downy mildew of opium poppy using hyperspectral and thermal UAV imagery

NASA Astrophysics Data System (ADS)

Calderón Madrid, Rocío; Navas Cortés, Juan Antonio; Montes Borrego, Miguel; Landa del Castillo, Blanca Beatriz; Lucena León, Carlos; Jesús Zarco Tejada, Pablo

2014-05-01

The present study explored the use of high-resolution thermal, multispectral and hyperspectral imagery as indicators of the infections caused by Verticillium wilt (VW) in olive trees and downy mildew (DM) in opium poppy fields. VW, caused by the soil-borne fungus Verticillium dahliae, and DM, caused by the biotrophic obligate oomycete Peronospora arborescens, are the most economically limiting diseases of olive trees and opium poppy, respectively, worldwide. V. dahliae infects the plant by the roots and colonizes its vascular system, blocking water flow and eventually inducing water stress. P. arborescens colonizes the mesophyll, appearing the first symptoms as small chlorotic leaf lesions, which can evolve to curled and thickened tissues and systemic infections that become deformed and necrotic as the disease develops. The work conducted to detect VW and DM infection consisted on the acquisition of time series of airborne thermal, multispectral and hyperspectral imagery using 2-m and 5-m wingspan electric Unmanned Aerial Vehicles (UAVs) in spring and summer of three consecutive years (2009 to 2011) for VW detection and on three dates in spring of 2009 for DM detection. Two 7-ha commercial olive orchards naturally infected with V. dahliae and two opium poppy field plots artificially infected by P. arborescens were flown. Concurrently to the airborne campaigns, olive orchards and opium poppy fields were assessed "in situ" to assess actual VW severity and DM incidence. Furthermore, field measurements were conducted at leaf and crown level. The field results related to VW detection showed a significant increase in crown temperature (Tc) minus air temperature (Ta) and a decrease in leaf stomatal conductance (G) as VW severity increased. This reduction in G was associated with a significant increase in the Photochemical Reflectance Index (PRI570) and a decrease in chlorophyll fluorescence. DM asymptomatic leaves showed significantly higher NDVI and lower green/red index
A Microgrant Supported Poppy Cultivation Renouncement Program for Afghanistan

DTIC Science & Technology

2009-02-17

the program will reduce the amount of opium produced. 2 History of Afghanistan Opium Production Poppy and opium have long played a role in Afghanistan’s...make enough money from growing wheat, saffron , or traditional farm crops to replace the income made from growing poppy. Farming education and attempts at...must run the program in order to build credibility for the government. History has shown that the population of Afghanistan does not support foreign
"Poppies are democracy!" A critical geopolitics of opium eradication and reintroduction in Turkey.

PubMed

Evered, Kyle T

2011-01-01

Historical scholarship in traditional geopolitics often relied on documents authored by states and by other influential actors. Although much work in the subfield of critical geopolitics thus far has addressed imbalances constructed in official, academic, and popular media due to a privileging of such narratives, priority might also be given to unearthing and bringing to light alternative geopolitical perspectives from otherwise marginalized populations. Utilizing the early-1970s case of the United States' first “war on drugs,” this article examines the geopolitics of opium-poppy eradication and its consequences within Turkey. Employing not only archival and secondary sources but also oral histories from now-retired poppy farmers, this study examines the diffusion of U.S. antinarcotics policies into the Anatolian countryside and the enduring impressions that the United States and Turkish government created. In doing so, this research gives voice to those farmers targeted by eradication policies and speaks more broadly to matters of narcotics control, sentiments of anti-Americanism, and notions of democracy in Turkey and the region, past and present.
Codeinone reductase isoforms with differential stability, efficiency and product selectivity in opium poppy.

PubMed

Dastmalchi, Mehran; Chang, Limei; Torres, Miguel A; Ng, Kenneth K S; Facchini, Peter J

2018-05-19

Codeinone reductase (COR) catalyzes the reversible NADPH-dependent reduction of codeinone to codeine as the penultimate step of morphine biosynthesis in opium poppy (Papaver somniferum). COR also irreversibly reduces neopinone, which forms by spontaneous isomerization in aqueous solution from codeinone, to neopine. In a parallel pathway involving 3-O-desmethylated analogs, COR converts morphinone to morphine, and neomorphinone to neomorphine. Similar to neopine, neomorphine formation by COR is irreversible. Neopine is a minor substrate for codeine O-demethylase (CODM) yielding morphine. In the plant, neopine levels are low and neomorphine has not been detected. Silencing of CODM leads to accumulation of upstream metabolites, such as codeine and thebaine, but does not result in a shift towards higher relative concentrations of neopine, suggesting a plant mechanism for limiting neopine production. In yeast (Saccharomyces cerevisiae) engineered to produce opiate alkaloids, the catalytic properties of COR lead to accumulation of neopine and neomorphine as major products. An isoform (COR-B) was isolated from opium poppy chemotype Bea's Choice that showed higher catalytic activity compared with previously characterized CORs, and it yielded mostly neopine in vitro and in engineered yeast. Five catalytically distinct COR isoforms (COR1.1-1.4 and COR-B) were used to determine sequence-function relationships that influence product selectivity. Biochemical characterization and site-directed mutagenesis of native COR isoforms identified four residues (V25, K41, F129 and W279) that affected protein stability, reaction velocity, and product selectivity and output. Improving COR performance coupled with an ability to guide pathway flux is necessary to facilitate production of opiate alkaloids in engineered microorganisms. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
The Environmental footprint of morphine: a life cycle assessment from opium poppy farming to the packaged drug

PubMed Central

McAlister, Scott; Ou, Yanjun; Neff, Elise; Hapgood, Karen; Story, David; Mealey, Philip; McGain, Forbes

2016-01-01

Objective To examine the environmental life cycle from poppy farming through to production of 100 mg in 100 mL of intravenous morphine (standard infusion bag). Design ‘Cradle-to-grave’ process-based life cycle assessment (observational). Settings Australian opium poppy farms, and facilities for pelletising, manufacturing morphine, and sterilising and packaging bags of morphine. Main outcome measures The environmental effects (eg, CO2 equivalent (‘CO2 e’) emissions and water use) of producing 100 mg of morphine. All aspects of morphine production from poppy farming, pelletising, bulk morphine manufacture through to final formulation. Industry-sourced and inventory-sourced databases were used for most inputs. Results Morphine sulfate (100 mg in 100 mL) had a climate change effect of 204 g CO2 e (95% CI 189 to 280 g CO2 e), approximating the CO2 e emissions of driving an average car 1 km. Water use was 7.8 L (95% CI 6.7– to 9.0 L), primarily stemming from farming (6.7 L). All other environmental effects were minor and several orders of magnitude less than CO2 e emissions and water use. Almost 90% of CO2 e emissions occurred during the final stages of 100 mg of morphine manufacture. Morphine's packaging contributed 95 g CO2 e, which accounted for 46% of the total CO2 e (95% CI 82 to 155 g CO2 e). Mixing, filling and sterilisation of 100 mg morphine bags added a further 86 g CO2 e, which accounted for 42% (95% CI 80 to 92 g CO2 e). Poppy farming (6 g CO2 e, 3%), pelletising and manufacturing (18 g CO2 e, 9%) made smaller contributions to CO2 emissions. Conclusions The environmental effects of growing opium poppies and manufacturing bulk morphine were small. The final stages of morphine production, particularly sterilisation and packaging, contributed to almost 90% of morphine's carbon footprint. Focused measures to improve the energy efficiency and sources for drug sterilisation and packaging could be explored as these are
The Environmental footprint of morphine: a life cycle assessment from opium poppy farming to the packaged drug.

PubMed

McAlister, Scott; Ou, Yanjun; Neff, Elise; Hapgood, Karen; Story, David; Mealey, Philip; McGain, Forbes

2016-10-21

To examine the environmental life cycle from poppy farming through to production of 100 mg in 100 mL of intravenous morphine (standard infusion bag). 'Cradle-to-grave' process-based life cycle assessment (observational). Australian opium poppy farms, and facilities for pelletising, manufacturing morphine, and sterilising and packaging bags of morphine. The environmental effects (eg, CO 2 equivalent ('CO 2 e') emissions and water use) of producing 100 mg of morphine. All aspects of morphine production from poppy farming, pelletising, bulk morphine manufacture through to final formulation. Industry-sourced and inventory-sourced databases were used for most inputs. Morphine sulfate (100 mg in 100 mL) had a climate change effect of 204 g CO 2 e (95% CI 189 to 280 g CO 2 e), approximating the CO 2 e emissions of driving an average car 1 km. Water use was 7.8 L (95% CI 6.7- to 9.0 L), primarily stemming from farming (6.7 L). All other environmental effects were minor and several orders of magnitude less than CO 2 e emissions and water use. Almost 90% of CO 2 e emissions occurred during the final stages of 100 mg of morphine manufacture. Morphine's packaging contributed 95 g CO 2 e, which accounted for 46% of the total CO 2 e (95% CI 82 to 155 g CO 2 e). Mixing, filling and sterilisation of 100 mg morphine bags added a further 86 g CO 2 e, which accounted for 42% (95% CI 80 to 92 g CO 2 e). Poppy farming (6 g CO 2 e, 3%), pelletising and manufacturing (18 g CO 2 e, 9%) made smaller contributions to CO 2 emissions. The environmental effects of growing opium poppies and manufacturing bulk morphine were small. The final stages of morphine production, particularly sterilisation and packaging, contributed to almost 90% of morphine's carbon footprint. Focused measures to improve the energy efficiency and sources for drug sterilisation and packaging could be explored as these are relevant to all drugs. Comparisons of the environmental
Simulating the Afghanistan-Pakistan opium supply chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watkins, Jennifer H; MacKerrow, Edward P; Merritt, Terence M

2010-04-08

This paper outlines an opium supply chain using the Hilmand province of Afghanistan as exemplar. The opium supply chain model follows the transformation of opium poppy seed through cultivation and chemical alteration to brown heroin base. The purpose of modeling and simulating the Afghanistan-Pakistan opium supply chain is to discover and test strategies that will disrupt this criminal enterprise.
Dioxygenases Catalyze O-Demethylation and O,O-Demethylenation with Widespread Roles in Benzylisoquinoline Alkaloid Metabolism in Opium Poppy*

PubMed Central

Farrow, Scott C.; Facchini, Peter J.

2013-01-01

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy. PMID:23928311
Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy.

PubMed

Farrow, Scott C; Facchini, Peter J

2013-10-04

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain rhoeadine alkaloids in opium poppy.
Poppies for medicine in Afghanistan: lessons from India and Turkey.

PubMed

Windle, James

2011-01-01

This study examines India and Turkey as case studies relevant to the Senlis Council’s ‘poppies for medicine’ proposal. The proposal is that Afghan farmers are licensed to produce opium for medical and scientific purposes. Here it is posited that the Senlis proposal neglects at least three key lessons from the Turkish and Indian experiences. First, not enough weight has been given to diversion from licit markets, as experienced in India. Second, both India and Turkey had significantly more efficient state institutions with authority over the licensed growing areas. Third, the proposal appears to overlook the fact that Turkey’s successful transition was largely due to the use of the poppy straw method of opium production. It is concluded that, while innovative and creative policy proposals such as that of the Senlis proposal are required if Afghanistan is to move beyond its present problems, ‘poppies for medicine’ does not withstand evidence-based scrutiny.
Straightforward analytical method to determine opium alkaloids in poppy seeds and bakery products.

PubMed

López, Patricia; Pereboom-de Fauw, Diana P K H; Mulder, Patrick P J; Spanjer, Martien; de Stoppelaar, Joyce; Mol, Hans G J; de Nijs, Monique

2018-03-01

A straightforward method to determine the content of six opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine and narceine) in poppy seeds and bakery products was developed and validated down to a limit of quantification (LOQ) of 0.1mg/kg. The method was based on extraction with acetonitrile/water/formic acid, ten-fold dilution and analysis by LC-MS/MS using a pH 10 carbonate buffer. The method was applied for the analysis of 41 samples collected in 2015 in the Netherlands and Germany. All samples contained morphine ranging from 0.2 to 240mg/kg. The levels of codeine and thebaine ranged from below LOQ to 348mg/kg and from below LOQ to 106mg/kg, respectively. Sixty percent of the samples exceeded the guidance reference value of 4mg/kg of morphine set by BfR in Germany, whereas 25% of the samples did not comply with the limits set for morphine, codeine, thebaine and noscapine by Hungarian legislation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Hector Berlioz and other famous artists with opium abuse.

PubMed

Wolf, Paul L

2010-01-01

The effect of opium on the creativity and productivity of a famous composer of classical music, an essayist, and poets including Hector Berlioz, Thomas De Quincy, Samuel Taylor Coleridge, John Keats, and Jean Cocteau, is described. Opium is a narcotic drug prepared from the juice of the unripe seed capsules of the opium poppy. It contains alkaloids such as morphine, codeine, and papaverine. Medically it is used to relieve pain and produce sleep. It is used as an intoxicant. Alcohol and opium were commonly relied on in the 19th century, especially by artists, to stimulate creativity and relieve stress. These artists described the effect of opium on their creativity and productivity. Copyright (c) 2010 S. Karger AG, Basel.

Opium induces apoptosis in jurkat cells.

PubMed

Igder, Somayeh; Asadikaram, Gholam Reza; Sheykholeslam, Farzaneh; Sayadi, Ahmad Reza; Mahmoodi, Mehdi; Kazemi Arababadi, Mohammad; Rasaee, Mohammad Javad

2013-01-01

The direct effect of some opioids on immune cells has been demonstrated. The aim of this study was to assess the apoptotic effect of opium on Jurkat T lymphocyte cells. Different concentrations of opium (2.86 × 10-3 to 2.86 × 10-11 g/ml) were added to 24-well plates containing 5 × 105 Jurkat cells. Apoptotic events were assessed after 6, 24, and 72 hours by flow-cytometric detection of surface phosphatidylserine. Significant differences in apoptosis of Jurkat cells were seen at 24 and 72 hours in different concentrations of opium (P < 0.05). After 72 hours, significant increase in necrosis of Jurkat cells was seen in opium concentration of 2.85 × 10-3 g/ml compared to cells without opium (control) (P < 0.05). These results showed that opium directly increases apoptosis and necrosis of T lymphocytes. This effect may play a role in immune dysfunction in opium addicts.
Opium Induces Apoptosis in Jurkat Cells

PubMed Central

Igder, Somayeh; Asadikaram, Gholam Reza; Sheykholeslam, Farzaneh; Sayadi, Ahmad Reza; Mahmoodi, Mehdi; Kazemi Arababadi, Mohammad; Rasaee, Mohammad Javad

2013-01-01

Background The direct effect of some opioids on immune cells has been demonstrated. The aim of this study was to assess the apoptotic effect of opium on Jurkat T lymphocyte cells. Methods Different concentrations of opium (2.86 × 10-3 to 2.86 × 10-11 g/ml) were added to 24-well plates containing 5 × 105 Jurkat cells. Apoptotic events were assessed after 6, 24, and 72 hours by flow-cytometric detection of surface phosphatidylserine. Findings Significant differences in apoptosis of Jurkat cells were seen at 24 and 72 hours in different concentrations of opium (P < 0.05). After 72 hours, significant increase in necrosis of Jurkat cells was seen in opium concentration of 2.85 × 10-3 g/ml compared to cells without opium (control) (P < 0.05). Conclusion These results showed that opium directly increases apoptosis and necrosis of T lymphocytes. This effect may play a role in immune dysfunction in opium addicts. PMID:24494155
Atomic Structure of Salutaridine Reductase from the Opium Poppy (Papaver somniferum)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higashi, Yasuhiro; Kutchan, Toni M.; Smith, Thomas J.

The opium poppy (Papaver somniferum L.) is one of the oldest known medicinal plants. In the biosynthetic pathway for morphine and codeine, salutaridine is reduced to salutaridinol by salutaridine reductase (SalR; EC 1.1.1.248) using NADPH as coenzyme. Here, we report the atomic structure of SalR to a resolution of {approx}1.9 {angstrom} in the presence of NADPH. The core structure is highly homologous to other members of the short chain dehydrogenase/reductase family. The major difference is that the nicotinamide moiety and the substrate-binding pocket are covered by a loop (residues 265-279), on top of which lies a large 'flap'-like domain (residuesmore » 105-140). This configuration appears to be a combination of the two common structural themes found in other members of the short chain dehydrogenase/reductase family. Previous modeling studies suggested that substrate inhibition is due to mutually exclusive productive and nonproductive modes of substrate binding in the active site. This model was tested via site-directed mutagenesis, and a number of these mutations abrogated substrate inhibition. However, the atomic structure of SalR shows that these mutated residues are instead distributed over a wide area of the enzyme, and many are not in the active site. To explain how residues distal to the active site might affect catalysis, a model is presented whereby SalR may undergo significant conformational changes during catalytic turnover.« less
Combating Opium in Afghanistan. Strategic Forum, Number 224, November 2006

DTIC Science & Technology

2006-11-01

strategy will be severely limited.17 Truffles, a fungi delicacy, are the only legal agricultural product whose value rivals that of opium poppy...to bear fruit and are not viable sources of income over the short term. Wheat , a favorite substitute of Western aid agencies, does not provide a...viable alternative for farmers. Income from poppy production is approximately $5,400 per hectare, while wheat brings in $500. Farmers claim that
Poppies or Peace: The Relationship between Opium Production and Conflict

DTIC Science & Technology

2012-06-08

GDP’s inability to reflect individual well- being or the environmental impact of economic growth, rather than criticizing GDP for its ability to...regulate or restrict the opium trade. For the “substantial corpus of international legislation controlling opium and its derivatives . . . the main...
Lethal Lullabies: A History of Opium Use in Infants.

PubMed

Obladen, Michael

2016-02-01

Poppy extract accompanied the human infant for more than 3 millenia. Motives for its use included excessive crying, suspected pain, and diarrhea. In antiquity, infantile sleeplessness was regarded as a disease. When treatment with opium was recommended by Galen, Rhazes, and Avicenna, baby sedation made its way into early medical treatises and pediatric instructions. Dabbing maternal nipples with bitter substances and drugging the infant with opium were used to hasten weaning. A freerider of gum lancing, opiates joined the treatment of difficult teething in the 17th century. Foundling hospitals and wet-nurses used them extensively. With industrialization, private use was rampant among the working class. In German-speaking countries, poppy extracts were administered in soups and pacifiers. In English-speaking countries, proprietary drugs containing opium were marketed under names such as soothers, nostrums, anodynes, cordials, preservatives, and specifics and sold at the doorstep or in grocery stores. Opium's toxicity for infants was common knowledge; thousands of cases of lethal intoxication had been reported from antiquity. What is remarkable is that the willingness to use it in infants persisted and that physicians continued to prescribe it for babies. Unregulated trade, and even that protected by governments, led to greatly increased private use of opiates during the 19th century. Intoxication became a significant factor in infant mortality. As late as 1912, the International Hague Convention forced governments to implement legislation that effectively curtailed access to opium and broke the dangerous habit of sedating infants. © The Author(s) 2015.
Opium Field Detection in South Oxfordshire Using SAR Polarimetry

NASA Astrophysics Data System (ADS)

Walker, Nick; Marino, Armando

2011-03-01

To-date the use of satellite imagery to monitor the growth of illicit crops such as marijuana, opium and coca has mostly been conducted using optical frequencies. However, it is well known that while optical imagery can be hampered by localised aerosols such as thin clouds, cirrus, haze and smoke, these do not present a problem for Synthetic Aperture Radar (SAR). In recent years a new generation of satellite borne sensors have also been equipped with enhanced polarimetric capabilities, which can potentially help with detecting and classifying different terrain types. For these reasons we believe it is useful to consider whether high resolution polarimetric SAR data can be applied to illicit crop detection.In this paper we present the results of an experiment whereby opium poppy fields were successfully detected in the south Oxfordshire region in the UK using RadarSat-2 quad-polarisation imagery. It should be noted that these crops are not being grown illicitly but instead are being cultivated for medicinal reasons in parts of the UK. It is interesting to note that the poppies cultivated for opium in the UK have white flowers rather than the more familiar red as can be seen from the photograph in Figure 1, which was taken 11 days earlier in the season compared to Figure 4 and Figure 5.
[The use of opium in Roman society and the dependence of Princeps Marcus Aurelius].

PubMed

Trancas, Bruno; Borja Santos, Nuno; Patrício, Luís D

2008-01-01

Opium was known and frequently used in Roman society. Medical practice recognized its usefulness as an analgesic, soporific, anti-tussic or anti-diarrheic agent, as well as other currently unsupported uses with quasi-magical properties. It was additionally used as an ingredient in antidotes, panaceas and poisons. The authors present a non-exhaustive compilation of opium use according to medical doctors, writers and encyclopaedists of the time. Mythological and literary representations of the opium poppy reflected its diverse roles, being associated with prosperity and fertility, sleep, death and the underworld and with the art of medicine. Despite its free and routine use, there is no solid evidence of addiction, except the putative case of emperor Marcus Aurelius, consistently reported as one of the most likely cases of addiction to opium.
Trace and major element levels in rats after oral administration of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) seeds.

PubMed

Aksoy, Laçine; Sözbilir, Nalan Bayşu

2015-10-01

The study investigated the toxic effects of diesel and biodiesel derived from opium poppy (Papaver somniferum L.) oil seeds on the trace and major elements in kidney, lung, liver, and serum of rats. By the end of 21 days, trace and major element concentrations in kidney, lung, and liver tissues and the serum were measured using inductively coupled plasma-optical emission spectroscopy. We observed that trace and major element levels in kidney, lung, and liver tissues and the serum changed. Especially, important differences were detected in trace and major element concentrations in kidney and lung tissues. In kidney tissue, the concentration differences of calcium, sodium, and zinc (Zn) were found between diesel and biodiesel groups. In lung tissue, the concentration differences of cadmium, lithium, magnesium, manganese, and Zn were found between diesel and biodiesel groups. Among the significant findings, Zn concentration in serum and liver tissue of diesel and biodiesel were different from control (p < 0.05). However, the metal levels of biodiesel group were similar to control group. Due to lesser toxicity of biodiesel, it could be considered as an alternate fuel. © The Author(s) 2013.
Determination of inorganic elements in poppy straw by scanning electron microscopy with energy dispersive spectrometry as a means of ascertaining origin.

PubMed

Copur, E; Göger, N G; Orbey, T; Sener, B

2005-01-01

Cultivation of poppy as a source of opium alkaloids for legitimate medical purposes has a long tradition in Turkey. The main products are poppy straw and concentrate of poppy straw, obtained from dried poppy capsules. The aims of the study reported in the present article were to establish inorganic element profiles for the poppy-growing provinces of Turkey by means of x-ray analysis by scanning electron microscopy with energy dispersive spectrometry (SEM/EDS) and to explore the potential of the technique for determination of origin. Ten elements (sodium, magnesium, silicon, phosphorus, sulphur, chlorine, potassium, calcium, copper and zinc) were analysed in poppy straw samples from 67 towns in nine provinces. As regards the determination of origin, the most significant finding was the presence of copper and zinc in the poppy straw samples from 8 of the 15 towns in Afyon Province. Since those elements are not normally found in soil, it is assumed that their presence is the result of environmental (industrial) contamination. Differences in the samples from the other eight provinces were less significant, possibly a result of their geographical proximity. Nevertheless, differences in the samples were apparent. Because the findings are relative rather than absolute in terms of presence or absence of individual inorganic elements, further research is required to convert them into operationally usable results. The inorganic element profiles generated in the study have been used to form the basis for the development of a comprehensive database on poppy straw samples, which may be used in comparing samples and determining their origin.
77 FR 70824 - Importer of Controlled Substances; Notice of Application; Johnson Matthey, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

... Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw...-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. Comments and...
Socio-climatic Exposure of an Afghan Poppy Farmer

NASA Astrophysics Data System (ADS)

Mankin, J. S.; Diffenbaugh, N. S.

2011-12-01

Many posit that climate impacts from anthropogenic greenhouse gas emissions will have consequences for the natural and agricultural systems on which humans rely for food, energy, and livelihoods, and therefore, on stability and human security. However, many of the potential mechanisms of action in climate impacts and human systems response, as well as the differential vulnerabilities of such systems, remain underexplored and unquantified. Here I present two initial steps necessary to characterize and quantify the consequences of climate change for farmer livelihood in Afghanistan, given both climate impacts and farmer vulnerabilities. The first is a conceptual model mapping the potential relationships between Afghanistan's climate, the winter agricultural season, and the country's political economy of violence and instability. The second is a utility-based decision model for assessing farmer response sensitivity to various climate impacts based on crop sensitivities. A farmer's winter planting decision can be modeled roughly as a tradeoff between cultivating the two crops that dominate the winter growing season-opium poppy (a climate tolerant cash crop) and wheat (a climatically vulnerable crop grown for household consumption). Early sensitivity analysis results suggest that wheat yield dominates farmer decision making variability; however, such initial results may dependent on the relative parameter ranges of wheat and poppy yields. Importantly though, the variance in Afghanistan's winter harvest yields of poppy and wheat is tightly linked to household livelihood and thus, is indirectly connected to the wider instability and insecurity within the country. This initial analysis motivates my focused research on the sensitivity of these crops to climate variability in order to project farmer well-being and decision sensitivity in a warmer world.
Detection of Papaverine for the Possible Identification of Illicit Opium Cultivation.

PubMed

Mirsafavi, Rustin Y; Lai, Kristine; Kline, Neal D; Fountain, Augustus W; Meinhart, Carl D; Moskovits, Martin

2017-02-07

Papaverine is a non-narcotic alkaloid found endemically and uniquely in the latex of the opium poppy. It is normally refined out of the opioids that the latex is typically collected for, hence its presence in a sample is strong prima facie evidence that the carrier from whom the sample was collected is implicated in the mass cultivation of poppies or the collection and handling of their latex. We describe an analysis technique combining surface-enhanced Raman spectroscopy (SERS) with microfluidics for detecting papaverine at low concentrations and show that its SERS spectrum has unique spectroscopic features that allows its detection at low concentrations among typical opioids. The analysis requires approximately 2.5 min from sample loading to results, which is compatible with field use. The weak acid properties of papaverine hydrochloride were investigated, and Raman bands belonging to the protonated and unprotonated forms of the isoquinoline ring of papaverine were identified.
76 FR 77253 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... Schedule Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw...-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. Comments and...
Disentangling Peronospora on Papaver: Phylogenetics, Taxonomy, Nomenclature and Host Range of Downy Mildew of Opium Poppy (Papaver somniferum) and Related Species

PubMed Central

Voglmayr, Hermann; Montes-Borrego, Miguel; Landa, Blanca B.

2014-01-01

Based on sequence data from ITS rDNA, cox1 and cox2, six Peronospora species are recognised as phylogenetically distinct on various Papaver species. The host ranges of the four already described species P. arborescens, P. argemones, P. cristata and P. meconopsidis are clarified. Based on sequence data and morphology, two new species, P. apula and P. somniferi, are described from Papaver apulum and P. somniferum, respectively. The second Peronospora species parasitizing Papaver somniferum, that was only recently recorded as Peronospora cristata from Tasmania, is shown to represent a distinct taxon, P. meconopsidis, originally described from Meconopsis cambrica. It is shown that P. meconopsidis on Papaver somniferum is also present and widespread in Europe and Asia, but has been overlooked due to confusion with P. somniferi and due to less prominent, localized disease symptoms. Oospores are reported for the first time for P. meconopsidis from Asian collections on Papaver somniferum. Morphological descriptions, illustrations and a key are provided for all described Peronospora species on Papaver. cox1 and cox2 sequence data are confirmed as equally good barcoding loci for reliable Peronospora species identification, whereas ITS rDNA does sometimes not resolve species boundaries. Molecular phylogenetic data reveal high host specificity of Peronospora on Papaver, which has the important phytopathological implication that wild Papaver spp. cannot play any role as primary inoculum source for downy mildew epidemics in cultivated opium poppy crops. PMID:24806292
76 FR 62447 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... registration as an importer of the following basic classes of controlled substances: Drug Schedule Opium, raw (9600) II Poppy Straw Concentrate (9670) II The company plans to import narcotic raw materials for... several controlled substances that are manufactured from raw opium, poppy straw, and concentrate of poppy...
76 FR 17967 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... basic classes of controlled substances: Drug Schedule Raw Opium (9600) II Concentrate of Poppy Straw (9670) II The company plans to import narcotic raw materials for manufacturing and further distribution... substances that are manufactured from raw opium, poppy straw, and concentrate of poppy straw. No comments or...
75 FR 32506 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... of controlled substances listed in schedule II: Drug Schedule Raw Opium (9600) II Concentrate of Poppy Straw (9670) II The company plans to import narcotic raw materials for manufacturing and further... substances that are manufactured from raw opium, poppy straw, and concentrate of poppy straw. No comments or...
75 FR 64743 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... Phenylacetone (8501) II Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II... re-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. As...
77 FR 5846 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... following basic classes of controlled substances: Drug Schedule Opium, raw (9600) II Poppy Straw Concentrate (9670) II The company plans to import narcotic raw materials for manufacturing and further distribution... substances that are manufactured from opium, raw, and poppy straw concentrate. Comments and requests for...

77 FR 60143 - Importer of Controlled Substances; Notice of Registration; Cody Laboratories, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... importer of the following basic classes of controlled substances: Drug Schedule Opium, raw (9600) II Concentrate Poppy Straw (9670) II Tapentadol (9780) II The company plans to import narcotic raw materials for... several controlled substances that are manufactured from opium raw, and poppy straw concentrate. The...
75 FR 65658 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... Raw Opium (9600) II Concentrate of Poppy Straw (9670) II The company plans to import narcotic raw... a manufacturer of several controlled substances that are manufactured from raw opium, poppy straw... narcotic raw material are not appropriate. As noted in a previous notice published in the Federal Register...
Norcoclaurine synthase is a member of the pathogenesis-related 10/Bet v1 protein family.

PubMed

Lee, Eun-Jeong; Facchini, Peter

2010-10-01

Norcoclaurine synthase (NCS) catalyzes the first committed step in the biosynthesis of benzylisoquinoline alkaloids (BIAs). NCS from Thalictrum flavum (Tf NCS), Papaver somniferum (Ps NCS1 and Ps NCS2), and Coptis japonica (Cj PR10A) share substantial identity with pathogen-related 10 (PR10) and Bet v1 proteins, whose functions are not well understood. A distinct enzyme (Cj NCS1) with similarity to 2-oxoglutarate-dependent dioxygenases was suggested as the bona fide NCS in C. japonica. Here, we validate the exclusive role of PR10/Bet v1-type NCS enzymes in BIA metabolism. Immunolocalization of Ps NCS2 revealed its cell type-specific occurrence in phloem sieve elements, which contain all other known BIA biosynthetic enzymes. In opium poppy, NCS transcripts and proteins were abundant in root and stem, but at low levels in leaf and carpel. Silencing of NCS in opium poppy profoundly reduced alkaloid levels compared with controls. Immunoprecipitation of NCS from total protein extracts of T. flavum cells resulted in a nearly complete attenuation of NCS activity. A Ps NCS2-green fluorescent protein fusion introduced by microprojectile bombardment into opium poppy cells initially localized to the endoplasmic reticulum but subsequently sorted to the vacuole. In our hands, Cj NCS1 did not catalyze the formation of (S)-norcoclaurine from dopamine and 4-hydroxyphenylacetaldehyde.
Principal opium alkaloids as possible biochemical markers for the source identification of Indian opium.

PubMed

Mohana, Mudiam; Reddy, Krishna; Jayshanker, Gurumurthy; Suresh, Velayudhan; Sarin, Rajendra Kumar; Sashidhar, R B

2005-08-01

A total of 124 opium samples originating from different licit opium growing divisions of India were analyzed for their principal alkaloid (thebaine, codeine, morphine, papaverine, and narcotine) content by capillary zone electrophoresis (CZE) without derivatization or purification. Absence of papaverine in Bareilly, Tilhar, and most of the samples originating from Kota is a significant observation in relation to the source of Indian opium. Multiple discriminant analysis was applied to the quantitative principal alkaloid data to determine an optimal classifier in order to evaluate the source of Indian opium. The predictive value based on the discriminant analysis was found to be 85% in relation to the source of opium and the study also revealed that all the principal alkaloids have to be analyzed for source identification of Indian opium. Chemometrics performed with principal alkaloids analytical data was used successfully in discriminating the licit opium growing divisions of India into three major groups, viz., group I, II, and III. The methodology developed may find wide forensic application in identifying the source of licit or illicit opium originating from India, and to differentiate it from opium originating from other opium producing countries.
The rules of drug taking: wine and poppy derivatives in the ancient world. VII. A ritual use of poppy derivatives?

PubMed

Nencini, P

1997-08-01

Besides fertility, poppies have been used to symbolize sleep, night, and death. Consistent with the agrarian origin of their ritual use, poppies also became a symbol of reincarnation. Several literary and iconographic sources, in particular of the early Roman imperial age, are here interpreted as evidence that poppy derivatives were ingested during mystery rites. The reversible narcotic effects of poppy derivatives should have allowed a "realistic" representation of death and reincarnation, as intended by the Orphic belief of the transmigration of souls.
[Milk of paradise? Opium and opiates in nineteenth and twentieth century literature].

PubMed

Schäfer, D

2007-08-01

One cannot have an idea of this multifaceted theme without its medical and cultural-historical background. After a history of several thousand years as a remedy and consumer good, around 1800 this poppy drug was in the focus of public attention due to Brownianism, at first as an often self-prescribed unspecific remedy against physical and mental pain. Many representatives of the early Romanticism knew it from personal experience. However, it was the publication of Thomas de Quincey's Confessions of an English Opium-Eater (1821/1822) which made it a subject of international debate in accordance with the programmatic statements of writers of that epoque and corresponding to the antibourgeois attitude of these men. It became a motif of a counter-world experience and a subject and cause of lyric-subjective reflection as well as a possible premise of poetic creativity.
76 FR 5827 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

... basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Coca Leaves (9040) II... re-registration to import crude opium, poppy straw, concentrate of poppy straw or coca leaves. As...
77 FR 4831 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-31

... (8501) II Coca Leaves (9040) II Oxycodone (9143) II Hydromorphone (9150) II Hydrocodone (9193) II... crude opium, poppy straw, poppy straw concentrate, and coca leaves. As explained in the Correction to...
75 FR 1812 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... of controlled substances listed in schedule II: Drug Schedule Phenylacetone (8501) II Coca Leaves... registration or re-registration to import crude opium, poppy straw, concentrate of poppy straw or coca leaves...
75 FR 69705 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... re-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves. As... classes of controlled substances listed in schedule I or II, which fall under the authority of section...
76 FR 39123 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-05

... Carfentanil (9743) II Coca Leaves (9040) II Cocaine (9041) II Codeine (9050) II Dextropropoxyphene, bulk (non... registration or re-registration to import crude opium, poppy straw, concentrate of poppy straw, and coca leaves...
76 FR 35239 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... (9040) II Raw Opium (9600) II Poppy Straw (9650) II Concentrate of Poppy Straw (9670) II The company... narcotic raw material are not appropriate. As noted in a previous notice published in the Federal Register...
75 FR 22844 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... narcotic raw material are not appropriate. As noted in a previous notice published in the Federal Register... Coca Leaves (9040) II Raw Opium (9600) II Poppy Straw (9650) II Concentrate of Poppy Straw (9670) II...
77 FR 24983 - Importer of Controlled Substances; Notice of Application Penick Corporation

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... import narcotic raw material are not appropriate. 72 FR 3417(2007). As noted in a previous notice... Schedule Coca Leaves (9040) II Raw Opium (9600) II Poppy Straw (9650) II Concentrate of Poppy Straw (9670...
Effect of ground poppy seed as a fat replacer on meat burgers.

PubMed

Gök, Veli; Akkaya, Levent; Obuz, Ersel; Bulut, Sait

2011-12-01

Poppy seed paste was used in koefte production as an animal fat replacer and efficacy of using poppy seed was investigated. The use of ground poppy seed in formulation of meat burgers had no effect on the moisture content of uncooked meat burgers; however, it did have a significant effect (p<0.05) on the fat content of meat burgers. Ground poppy seed addition significantly affected (p<0.05) cooking yield, moisture retention, and fat retention of meat burgers. Ground poppy seed addition significantly decreased (p<0.05) saturated fatty acid contents as the amount of ground poppy seed increased in meat burgers. A strong significant decrease (p<0.05) on the cholesterol content of meat burgers with ground poppy seed addition was observed. Samples having 20% ground poppy seed had significantly better texture and juiciness score (p<0.05) than any other sample which could be explained by increased moisture retention. Replacing animal fat with ground poppy seed paste is effective and may pave the way for an innovative meat product. Copyright © 2011 Elsevier Ltd. All rights reserved.
Opiates in poppy seed: effect on urinalysis results after consumption of poppy seed cake-filling.

PubMed

Pettitt, B C; Dyszel, S M; Hood, L V

1987-07-01

We report the analysis of poppy seed filling for morphine and codeine content. Concentrations in the range 17.4 to 18.6 micrograms/g (morphine) and 2.3 to 2.5 micrograms/g (codeine) were found in different lots of the filling, which is widely used in baking. The effect of consumption of poppy seed filling on opiate urinalysis results is discussed. Morphine concentrations as high as 4.5 mg/L are reported, with persistence of concentrations greater than 0.3 mg/L as long as 35 h after consumption.
Poppy tea drinking in East Anglia.

PubMed

London, M; O'Regan, T; Aust, P; Stockford, A

1990-10-01

Poppy tea drinking was a widespread traditional practice in the Fenlands of East Anglia during the nineteenth century. The subsequent social changes which led to greater integration of the area with the rest of the country may have contributed to a decline in the practice. In recent years poppy tea drinking has been revived within the illicit drug using community and a survey using a self-report questionnaire was carried out among patients attending the Cambridge Drug Dependency Unit. Forty-three patients admitted to drinking poppy tea, usually during the summer months and on an intermittent basis. The potency of the infusion varied and was unpredictable but in general was low. Although poisoning from herbicides and pesticides was seen as the main risk, it is in the main perceived by drug users as a harmless secondary activity existing alongside the more regular and more potent drugs of misuse.
The Hidden Habit of the Entomopathogenic Fungus Beauveria bassiana: First Demonstration of Vertical Plant Transmission

PubMed Central

Quesada-Moraga, Enrique; López-Díaz, Cristina; Landa, Blanca Beatriz

2014-01-01

Beauveria bassiana strain 04/01-Tip, obtained from a larva of the opium poppy stem gall wasp Iraella luteipes (Hymenoptera; Cynipidae), endophytically colonizes opium poppy (Papaver somniferum L.) plants and protects them against this pest. The goal of this study was to monitor the dynamics of endophytic colonization of opium poppy by B. bassiana after the fungus was applied to the seed and to ascertain whether the fungus is transmitted vertically via seeds. Using a species-specific nested PCR protocol and DNA extracted from surface-sterilised leaf pieces or seeds of B. bassiana-inoculated opium poppy plants, the fungus was detected within the plant beginning at the growth stage of rosette building and them throughout the entire plant growth cycle (about 120–140 days after sowing). The fungus was also detected in seeds from 50% of the capsules sampled. Seeds that showed positive amplification for B. bassiana were planted in sterile soil and the endophyte was again detected in more than 42% of the plants sampled during all plant growth stages. Beauveria bassiana was transmitted to seeds in 25% of the plants from the second generation that formed a mature capsule. These results demonstrate for the first time the vertical transmission of an entomopathogenic fungus from endophytically colonised maternal plants. This information is crucial to better understand the ecological role of entomopathogenic fungi as plant endophytes and may allow development of a sustainable and cost effective strategy for I. luteipes management in P. somniferum. PMID:24551242
The hidden habit of the entomopathogenic fungus Beauveria bassiana: first demonstration of vertical plant transmission.

PubMed

Quesada-Moraga, Enrique; López-Díaz, Cristina; Landa, Blanca Beatriz

2014-01-01

Beauveria bassiana strain 04/01-Tip, obtained from a larva of the opium poppy stem gall wasp Iraella luteipes (Hymenoptera; Cynipidae), endophytically colonizes opium poppy (Papaver somniferum L.) plants and protects them against this pest. The goal of this study was to monitor the dynamics of endophytic colonization of opium poppy by B. bassiana after the fungus was applied to the seed and to ascertain whether the fungus is transmitted vertically via seeds. Using a species-specific nested PCR protocol and DNA extracted from surface-sterilised leaf pieces or seeds of B. bassiana-inoculated opium poppy plants, the fungus was detected within the plant beginning at the growth stage of rosette building and them throughout the entire plant growth cycle (about 120-140 days after sowing). The fungus was also detected in seeds from 50% of the capsules sampled. Seeds that showed positive amplification for B. bassiana were planted in sterile soil and the endophyte was again detected in more than 42% of the plants sampled during all plant growth stages. Beauveria bassiana was transmitted to seeds in 25% of the plants from the second generation that formed a mature capsule. These results demonstrate for the first time the vertical transmission of an entomopathogenic fungus from endophytically colonised maternal plants. This information is crucial to better understand the ecological role of entomopathogenic fungi as plant endophytes and may allow development of a sustainable and cost effective strategy for I. luteipes management in P. somniferum.
Gas chromatographic-mass spectrometric characterization of thebaol, an opium constituent, and its structural analogs.

PubMed

Megutnishvili, Levan; Todua, Nino; Stein, Stephen; Mikaia, Anzor

2018-05-18

A GC-MS method is described for the characterization of thebaol, a component of opium poppy. The method includes preliminary sample derivatization to TMS, TBDMS, TFA, PFP and HFB substituted products. Fragmentation of resulting derivatives is unique under electron ionization, and proceeds via consecutive loss of two radicals that violate the "even-electron rule". Peaks of [M-2CH 3 ] +. and [M-C 4 H 9 -CH 3 ] +. ions show maximum intensities in the spectra of trimethyl- and tert-butyldimethylsilyl-thebaols. Elimination of perfluoroalkyl and methyl radicals from M +. is characteristic for TFA, PFP and HFB thebaols. The same fragmentation peculiarity is characteristic for derivatives prepared from related natural compounds containing vicinal 2-methoxyphenol moieties. The unique fragmentation of trialkylsilyl and perfluoroacyl derivatives of thebaol can be successfully used for thebaol determination within complex mixtures. This is part 4 from the series "Analytical derivatives in mass spectrometry", parts 1, 2 and 3 see [1-3]. Copyright © 2018 Elsevier B.V. All rights reserved.

Production of Pharmaceuticals from Papaver Cultivars In Vitro

USDA-ARS?s Scientific Manuscript database

A methodology to clonally proliferate Iranian poppy (Papaver bracteatum Lindl.) and opium poppy (P. somniferum L.) shoots is presented employing an in vitro hydroponics system (i.e., automated plant culture system (APCS)). Temperature had a profound effect on growth and alkaloid production after 8-...
Effects of opium consumption on cardiometabolic diseases.

PubMed

Masoudkabir, Farzad; Sarrafzadegan, Nizal; Eisenberg, Mark J

2013-12-01

Opium is the second-most-commonly abused substance (after tobacco) in developing countries of the Middle East region, and in many Asian nations. One of the reasons for the high prevalence of opium abuse in these countries is a traditional belief among Eastern people, even including some medical staff, that opium might have beneficial effects on cardiovascular health and in the control of diabetes mellitus, hypertension, and dyslipidaemia. In this Perspectives article, we summarize the current understanding of the pharmacotoxicology of opium and its specific effects on glycaemic control, blood pressure, lipid profile, and atherosclerosis. On the basis of the available evidence, we believe not only that opium has no ameliorating effect on cardiovascular diseases, but also that the use of this drug might have adverse effects on these conditions. Therefore, people should be educated about the hazardous effects of opium consumption on cardiometabolic diseases.
"Vintage meds": a netnographic study of user decision-making, home preparation, and consumptive patterns of laudanum.

PubMed

Van Hout, Marie Claire; Hearne, Evelyn

2015-04-01

Reviews have commented on rising clandestine manufacture of opiate drug solutions for injecting, and to a lesser extent for oral use. Very little is known about user attempts to culture poppy seeds, widely available on the internet for manufacture of long acting medium-high potency oral solutions, both as poppy seed tea or as opium tincture (laudanum). A netnographic research methodology aimed to provide online consumer insight into user sourcing and decision influences, experiences of home manufacture of laudanum, utilization of opium tincture recipes, and consumptive patterns. A systematic internet search was conducted using the terms: "Laudanum," "Opium tincture," and "Tincture of Opium" in combination with "forum." Following screening of 810 forum threads with exclusion criteria and removal of duplicates, 75 fora threads on 6 online drug fora were analyzed using the empirical phenomenological psychological method. Four themes were generated. Findings illustrated the underpinning of user reminiscing about Victorian use of standardized laudanum, long duration shelf life, and medicinal use for opiate withdrawals with intentions to prepare. Preparation of famous recipes and use of authentic storage bottles boosted nostalgia. Participants appeared well versed in kitchen chemistry processes. Discussions centered on type and amount of alcohol used, use of additives to promote palatability and intoxication effect, homogenization of poppy seeds, and double extraction using opium tincture. Lack of detail available on intoxication experiences, with tentative dosage advised. Development of targeted and credible "counterpublic" harm reduction initiatives situated within online consumerism of communal drug knowledge is warranted.
77 FR 64142 - Importer of Controlled Substances, Notice of Application, Noramco, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-18

... following basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II Tapentadol (9780) II The company plans to import raw Opium (9600) and... substance. Comments and requests for hearings on applications to import narcotic raw material are not...
In-planta detection and monitorization of endophytic colonization by a Beauveria bassiana strain using a new-developed nested and quantitative PCR-based assay and confocal laser scanning microscopy.

PubMed

Landa, B B; López-Díaz, C; Jiménez-Fernández, D; Montes-Borrego, M; Muñoz-Ledesma, F J; Ortiz-Urquiza, A; Quesada-Moraga, E

2013-10-01

Beauveria bassiana strain 04/01-Tip obtained from larvae of the opium poppy stem gall Iraella luteipes endophytically colonizes opium poppy plants and protect it against this pest. Development of a specific, rapid and sensitive technique that allows accurately determining the process and factors leading to the establishment of this strain in opium poppy plants would be essential to achieve its efficient control in a large field scale. For that purpose in the present study, species-specific primers that can be used in conventional or quantitative PCR protocols were developed for specifically identification and detection of B. bassiana in plant tissues. The combination of the designed BB.fw/BB.rv primer set with the universal ITS1-F/ITS4 primer set in a two-step nested-PCR approach, has allowed the amplification of up to 10fg of B. bassiana. This represented an increase in sensitivity of 10000- and 1000-fold of detection than when using the BB.fw/BB.rv primers in a single or single-tube semi-nested PCR approaches, respectively. The BB.fw and BB.rv primer set were subsequently optimized to be used in real time quantitative PCR assays and allowed to accurately quantify B. bassiana DNA in different plant DNA backgrounds (leaves and seeds) without losing accuracy and efficiency. The qPCR protocol was used to monitor the endophytic colonization of opium poppy leaves byB. bassiana after inoculation with the strain EABb 04/01-Tip, detecting as low as 26fg of target DNA in leaves and a decrease in fungal biomass over time. PCR quantification data were supported in parallel with CLMS by the monitoring of spatial and temporal patterns of leaf and stem colonization using a GFP-tagged transformant of the B. bassiana EABb 04/01-Tip strain, which enabled to demonstrate that B. bassiana effectively colonizes aerial tissues of opium poppy plants mainly through intercellular spaces and even leaf trichomes. A decline in endophytic colonization was also observed by the last sampling
77 FR 31388 - Importer of Controlled Substances; Notice of Application; Noramco, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-25

... material are not appropriate. 72 FR 3417 (2007). In regard to the non-narcotic raw material, any bulk... following basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II Tapentadol (9780) II The company plans to import the raw Opium (9600...
75 FR 65658 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... basic classes of controlled substances listed in schedule II: Drug Schedule Raw Opium (9600) II Concentrate of Poppy Straw (9670) II Tapentadol (9780) II The company plans to import the Raw Opium (9600) and... Technologies, 72 FR 3417 (2007), comments and requests for hearings on applications to import narcotic raw...
Effect of Replacing Beef Fat with Poppy Seed Oil on Quality of Turkish Sucuk

PubMed Central

2015-01-01

Sucuk is the most popular dry-fermented meat product. Sucuk has a relatively high fat. Poppy seed oil as animal fat replacer was used in Turkish sucuk and effects of its use on sucuk quality were investigated. There was a significant (p<0.5) treatment × ripening time interaction for moisture, pH (p<0.05) and 2-thiobarbituric acid reactive substances (TBARS) values (p<0.01). Increasing poppy seed oil level decreased (p<0.05) TBARS values. Addition of poppy seed oil to the sucuks had a significant effect (p<0.01) on hardness, cohesiveness, gumminess, chewiness and springiness values. Cholesterol content of sucuks decreased (p<0.05) with poppy seed oil addition. Using pre-emulsified poppy seed oil as partial fat replacer in Turkish sucuk decreased cholesterol and saturated fatty acid content, but increased polyunsaturated fatty acids. Poppy seed oil as partial animal fat replacer in Turkish sucuk may have significant health benefits. PMID:26761834
Effect of Replacing Beef Fat with Poppy Seed Oil on Quality of Turkish Sucuk.

PubMed

Gök, Vel

2015-01-01

Sucuk is the most popular dry-fermented meat product. Sucuk has a relatively high fat. Poppy seed oil as animal fat replacer was used in Turkish sucuk and effects of its use on sucuk quality were investigated. There was a significant (p<0.5) treatment × ripening time interaction for moisture, pH (p<0.05) and 2-thiobarbituric acid reactive substances (TBARS) values (p<0.01). Increasing poppy seed oil level decreased (p<0.05) TBARS values. Addition of poppy seed oil to the sucuks had a significant effect (p<0.01) on hardness, cohesiveness, gumminess, chewiness and springiness values. Cholesterol content of sucuks decreased (p<0.05) with poppy seed oil addition. Using pre-emulsified poppy seed oil as partial fat replacer in Turkish sucuk decreased cholesterol and saturated fatty acid content, but increased polyunsaturated fatty acids. Poppy seed oil as partial animal fat replacer in Turkish sucuk may have significant health benefits.
More California-poppy in stubble field than in old field

Treesearch

Raymond D. Ratliff; Stanley E. Westfall; Richard W. Robarts

1972-01-01

The density and flowering of California-poppy (Eschscholzia californica var. peninsularis Green), amount of bare ground, and occurrence of other plants were studied in an old field and a stubble field near Madera, California. The stubble field had more poppy plants per unit of area, more plants flowering, and more bare ground than...
Urinary concentrations of morphine and codeine after consumption of poppy seeds.

PubMed

Thevis, Mario; Opfermann, Georg; Schänzer, Wilhelm

2003-01-01

A quantitative analysis of morphine and codeine in human urine was performed after oral intake of cakes containing commercially available poppy seeds in order to estimate the possibility of positive doping results. Therefore, eight products from different manufacturers (poppy seeds or baking mixtures) and origin were obtained and analyzed by gas chromatography-mass spectrometry for the presence of the alkaloids. One selected batch of poppy seeds was used as an ingredient in a typical cake and was the object of an excretion study with nine volunteers. After application, several urine specimens contained morphine with concentrations higher than 1 microg/mL, and peak values of approximately 10.0 microg/mL were detected. Because the International Olympic Committee set a cutoff limit for morphine at 1 microg/mL, high-performance athletes could possibly test positive in doping control after consumption of products containing poppy seeds.
The poppy seed test for colovesical fistula: big bang, little bucks!

PubMed

Kwon, Eric O; Armenakas, Noel A; Scharf, Stephen C; Panagopoulos, Georgia; Fracchia, John A

2008-04-01

Diagnosis of a colovesical fistula is often challenging, and usually involves numerous invasive and expensive tests and procedures. The poppy seed test stands out as an exception to this rule. We evaluated the accuracy and cost-effectiveness of various established diagnostic tests used to evaluate a suspected colovesical fistula. We identified 20 prospectively entered patients with surgically confirmed colovesical fistulas between 2000 and 2006. Each patient was evaluated preoperatively with a (51)chromium nuclear study, computerized tomography of the abdomen and pelvis with oral and intravenous contrast medium, and the poppy seed test. Costs were calculated using institutional charges, 2006 Medicare limiting approved charges and the market price, respectively. The z test was used to compare the proportion of patients who tested positive for a fistula with each of these modalities. The chromium study was positive in 16 of 20 patients (80%) at a cost of $490.83 per study. Computerized tomography was positive in 14 of 20 patients (70%) at a cost of $652.92 per study. The poppy seed test was positive in 20 of 20 patients (100%) at a cost of $5.37 per study. The difference in the proportion of patients who tested positive for a fistula on computerized tomography and the poppy seed test was statistically significant (p = 0.03). There was no difference between the chromium group and the computerized tomography or poppy seed group (p = 0.72 and 0.12, respectively). The poppy seed test is an accurate, convenient and inexpensive diagnostic test. It is an ideal initial consideration for evaluating a suspected colovesical fistula.
7 CFR 400.46 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Food Security Act of 1985, Implementation; Denial of Benefits... (erythroxylum coca), marijuana (cannabis satiua), opium poppies (papauer somniferum), and other drug-producing...
7 CFR 400.46 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Food Security Act of 1985, Implementation; Denial of Benefits... (erythroxylum coca), marijuana (cannabis satiua), opium poppies (papauer somniferum), and other drug-producing...
7 CFR 400.46 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Food Security Act of 1985, Implementation; Denial of Benefits... (erythroxylum coca), marijuana (cannabis satiua), opium poppies (papauer somniferum), and other drug-producing...
7 CFR 400.46 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Food Security Act of 1985, Implementation; Denial of Benefits... (erythroxylum coca), marijuana (cannabis satiua), opium poppies (papauer somniferum), and other drug-producing...
7 CFR 400.46 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE GENERAL ADMINISTRATIVE REGULATIONS Food Security Act of 1985, Implementation; Denial of Benefits... (erythroxylum coca), marijuana (cannabis satiua), opium poppies (papauer somniferum), and other drug-producing...
Opium and Afghanistan: Reassessing U.S. Counternarcotics Strategy

DTIC Science & Technology

2007-10-01

term security, development, and effective governance of Afghanistan.”3 This paper examines the nature of the opium problem in Afghanistan and...worldwide from opium for medical purposes.12 Opium is also refined for use in legal prescription painkillers such as OxyContin and Vicodin.13 However...will now be explored in detail. Lack of Security. The security situation in much of Afghanistan is simply inadequate to carry out an effective
Tall Poppies: Bullying Behaviors Faced by Australian High-Performance School-Age Athletes

ERIC Educational Resources Information Center

O'Neill, Maureen; Calder, Angela; Allen, Bill

2014-01-01

Little is known about Australian high-performance school-age athletes' experiences as victims of the tall poppy syndrome. Tall poppies are successful individuals bullied by those who are less successful in order to "normalize them." Nineteen current or previous national or international high-performance school-age athletes were…
76 FR 62447 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

... narcotic raw material are not appropriate. With regard to all non-Narcotic Raw Material drugs on this...-phenethyl-4-piperidine (8333)... II Phenylacetone (8501) II Opium, raw (9600) II Poppy Straw Concentrate...

78 FR 12101 - Importer of Controlled Substances; Notice of Application; Mallinckrodt, LLC.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... Coca Leaves (9040) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II The company plans to... or coca leaves. Comments and requests for hearings on applications to import narcotic raw material...
77 FR 19717 - Importer of Controlled Substances; Notice of Registration Mallinckrodt LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... raw material are not appropriate, 72 FR 3417 (2007). Regarding all other basic classes of controlled...) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II The company plans to import the listed...
77 FR 55503 - Importer of Controlled Substances; Notice of Registration; Cambrex Charles City, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

... hearings on applications to import narcotic raw material are not appropriate. 72 FR 3417 (2007). DEA has...-piperidine (8333).. II Phenylacetone (8501) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II The...
77 FR 24984 - Importer of Controlled Substances; Notice of Application; Rhodes Technologies

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

.... Comments and requests for hearings on applications to import narcotic raw material are not appropriate. 72... schedule II: Drug Schedule Opium, Raw (9600) II Poppy Straw Concentrate (9670) II The company plans to...
Afghanistan, poppies, and the global pain crisis.

PubMed

Clark, Peter A; Sillup, George P; Capo, Joseph A

2010-03-01

The World Health Organization has reported that somewhere between 30-86 million people suffer from moderate to severe pain due to cancer, HIV/AIDS, burns, wounds and other illnesses annually and do not have access to proper opiate anesthetics to control the pain [1]. The vast majority of these people live in poor nations where medicinal opiates are either too expensive or not readily available. In this paper, it is argued that access to adequate healthcare is a human right and that adequate healthcare includes management of pain. The solution to this problem may be in Afghanistan, a country now overwhelmed with poverty and war. Afghanistan is the world's leading producer of heroin. The increase in heroin production in Afghanistan has caused the United States and the international community to begin to eradicate Afghanistan's poppy fields leading to increased poverty among poppy farmers. This paper proposed a paradigm that can be implemented in Afghanistan which would allow for Afghan farmers to continue growing their poppy crop for medicinal opiates like morphine for poor nations. The paradigm covers all parameters of medicinal opiates production including licensing, security, cultivation, harvest, and factory production of medicinal opiates. The paradigm proposed is less expensive than eradication, brings honest income to Afghan farmers and the new Afghan nation, and can eventually lead to Afghanistan acquiring a respectable role in the world community. In closing, a full ethical analysis of the paradigm is included to justify the arguments made in the paper.
78 FR 19016 - Importer of Controlled Substances; Notice of Registration; Johnson Matthey, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... Schedule Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw Concentrate (9670) II The company plans to import the listed controlled substances as raw materials, to be...
76 FR 25374 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

...), comments and requests for hearings on applications to import narcotic raw material are not appropriate. As... Schedule Raw Opium (9600) I Concentrate of Poppy Straw (9670) II The company plans to import the listed...
78 FR 39337 - Importer of Controlled Substances; Notice Of Registration; Mallinckrodt, LLC.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... narcotic raw material are not appropriate, 72 FR 3417 (2007). Regarding Phenylacetone (8501), a basic class... Phenylacetone (8501) II Coca Leaves (9040) II Opium, raw (9600) II Poppy Straw Concentrate (9670) II The company...
75 FR 53718 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... 3417 (2007), comments and requests for hearings on applications to import narcotic raw material are not... Opium, raw (9600) II Poppy Straw Concentrate (9670) II The company plans to import the basic classes of...
78 FR 23594 - Importer of Controlled Substances; Notice of Application; Rhodes Technologies

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-19

... requests for hearings on applications to import narcotic raw material are not appropriate. 72 FR 3417 (2007... Schedule Opium, Raw (9600) II Poppy Straw Concentrate (9670) II The company plans to import the listed...
Opium and bladder cancer: A systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer

PubMed Central

Afshari, Mahdi; Janbabaei, Ghasem; Bahrami, Mohammad Amin

2017-01-01

Objective The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis. Methods The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3. Results We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05–4.87) and 5.7 (1.9–16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6–7.7). Conclusion This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It
Lessons in ambivalence: The Shanghai Municipal Council's opium policies, 1906-1917.

PubMed

Zhang, Yong-An; Du, Yilun

2016-11-01

Shanghai was considered to be a "capital of opium" in modern China, hence the history of opium in the city has received significant attention. In the Shanghai International Settlement, where Chinese and foreigners lived as neighbours, drugs were considered by the administration as both "trouble maker", and important financial resource. This paper explores how the Shanghai Municipal Council (SMC), the most senior governing body in the settlement, used its position to maximize political and economic profit from the trade and consumption of opium. The paper is based on documentary analysis of records of the SMC board meetings and other related material stored at Shanghai Municipal Archives. Interpretive approaches were used to analyze the shifting SMC strategies on opium consumption, the competing power relations and the way they were negotiated between actors with a stake in the region, including semi-colonialism and world systems analysis. With the dual purpose of preventing damage and enhancing municipal management, the SMC introduced a licensing system permitting the consumption and trade of drugs. However, the anti-opium policies of the late Qing government and the Anglo-Chinese 10 Year Agreement meant SMC had to shut down opium "houses" (opium dens) and "shops" (for the sale of opium to be consumed off the premises). Over almost a decade, the SMC shifted emphasis from political regulation of a social, recreational practice to maximizing financial benefit. In the process, SMC made full use of the opportunities it gained from a period of ambivalent Chinese and British power relations and local community rule. Copyright © 2016 Elsevier B.V. All rights reserved.
Abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction.

PubMed

Masoomi, Mohammad; Zare, Jahangir; Nasri, Hamidreza; Mirzazadeh, Ali; Sheikhvatan, Mehrdad

2011-04-01

A deleterious effect of withdrawal symptoms due to abrupt discontinuation of opium on the cardiovascular system is one of the recent interesting topics in the cardiovascular field. The current study hypothesized that the withdrawal syndrome due to discontinuing opium might be an important trigger for the appearance of acute myocardial infarction. Eighty-one opium-addicted individuals who were candidates for cardiovascular clinical evaluation and consecutively hospitalized in the coronary care unit (CCU) ward of Shafa Hospital in Kerman between January and July 2009 were included in the study and categorized in the case group, including patients experiencing withdrawal symptoms within 6-12 h after the reduced or discontinued use of opium according to the Diagnostic and Statistical Manual of Mental Disorders-revised IV version (DSM-IV-R) criteria for opium dependence and withdrawal, and the control group, without opium withdrawal symptoms. The appearance of acute myocardial infarction was compared between the two groups using multivariable regression models. Acute myocardial infarction occurred in 50.0% of those with withdrawal symptoms and in 45.1% of patients without evidence of opium withdrawal (P = 0.669). Multivariable analysis showed that opium withdrawal symptoms were not a trigger for acute myocardial infarction adjusting for demographic characteristics, marital status, education level and common coronary artery disease risk profiles [odds ratio (OR) = 0.920, 95% confidence interval (CI) = 0.350-2.419, P = 0.866]. Also, daily dose of opium before reducing or discontinuing use did not predict the appearance of myocardial infarction in the presence of confounder variables (OR = 0.975, 95% CI = 0.832-1.143, P = 0.755). Withdrawal syndrome due to abrupt discontinuation of opium does not have a triggering role for appearance of acute myocardial infarction.
76 FR 51400 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

... narcotic raw material are not appropriate. DEA has considered the factors in 21 U.S.C. 823(a) and 952(a... classes of controlled substances: Drug Schedule Raw Opium (9600) II Concentrate of Poppy Straw II (9670...
Mortality from respiratory diseases associated with opium use: a population-based cohort study.

PubMed

Rahmati, Atieh; Shakeri, Ramin; Khademi, Hooman; Poutschi, Hossein; Pourshams, Akram; Etemadi, Arash; Khoshnia, Masoud; Sohrabpour, Amir Ali; Aliasgari, Ali; Jafari, Elham; Islami, Farhad; Semnani, Shahryar; Gharravi, Abdolsamad; Abnet, Christian C; Pharoah, Paul D P; Brennan, Paul; Boffetta, Paolo; Dawsey, Sanford M; Malekzadeh, Reza; Kamangar, Farin

2017-11-01

Recent studies have suggested that opium use may increase mortality from cancer and cardiovascular diseases. However, no comprehensive study of opium use and mortality from respiratory diseases has been published. We aimed to study the association between opium use and mortality from respiratory disease using prospectively collected data. We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50 045 adults were enrolled from 2004 to 2008, and followed annually until June 2015, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest. During the follow-up period, 331 deaths from respiratory disease were reported (85 due to respiratory malignancies and 246 due to non-malignant aetiologies). Opium use was associated with an increased risk of death from any respiratory disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose-dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative opium use versus never use (P trend <0.001). The HRs (95% CI) for the associations between opium use and malignant and non-malignant causes of respiratory mortality were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively. Long-term opium use is associated with increased mortality from both malignant and non-malignant respiratory diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
75 FR 10312 - Importer of Controlled Substances Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-05

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances Notice of... by renewal to the Drug Enforcement Administration (DEA) to be registered as an importer of the basic classes of controlled substances listed in schedule II: Drug Schedule Opium, raw (9600) II Poppy Straw...
Correlates of opium use: retrospective analysis of a survey of tribal communities in Arunachal Pradesh, India

PubMed Central

2013-01-01

Background Household survey data of Changlang district, Arunachal Pradesh, were used in the present study to assess the prevalence of opium use among different tribes, and to examine the association between sociodemographic factors and opium use. Methods A sample of 3421 individuals (1795 men and 1626 women) aged 15 years and older was analyzed using a multivariate logistic regression model to determine factors associated with opium use. Sociodemographic information such as age, education, occupation, religion, ethnicity and marital status were included in the analysis. Results The prevalence of opium use was significantly higher (10.6%) among men than among women (2.1%). It varied according to age, educational level, occupation, marital status and religion of the respondents. In both sexes, opium use was significantly higher among Singpho and Khamti tribes compared with other tribes. Multivariate logistic regression indicated that opium use was significantly associated with age, occupation, ethnicity, religion and marital status of the respondents of both sexes. Multivariate rate ratios (MRR) for opium use were significantly higher (4–6 times) among older age groups (≥35 years) and male respondents. In males, the MRR was also significantly higher in respondents of Buddhist and Indigenous religion, while in females, the MRR was significantly higher in Buddhists. Most of the female opium users had taken opium for more than 5 years and were introduced to it by their husbands after marriage. Use of other substances among opium users comprised mainly tobacco (76%) and alcohol (44%). Conclusions The study reveals the sociodemographic factors, such as age, sex, ethnicity, religion and occupation, which are associated with opium use. Such information is useful for institution of intervention measures to reduce opium use. PMID:23575143
Recovery of thebaine and cryptopine from Indian opium.

PubMed

Ramanathan, V S; Chandra, P

1980-01-01

The thebaine content of the opium collected in the Madhya Pradesh region of India has been estimated and reported to range from 1.5 to 2.0 per cent. A technological process for the recovery of thebaine from the mother liquor remaining after the separation of natural codeine in the Government Opium and Alkaloid Works, Neemuch, has been developed in the laboratory and stepped up to an industrial scale. A method for the recovery to thebaine from the waste slaked-lime residues obtained from crude alkaloid cake mother liquor in the Government Opium and Alkaloid Works at Ghazipur has been worked out and the technical details of the process described. The recovery of thebaine would help to increase the production of codeine, and thebaine can also be used as a raw material for the manufacture of other drugs. Cryptopine has also been recovered from the mother liquor after the separation of thebaine.
Opium addiction in patients with coronary artery disease: a grounded theory study.

PubMed

Farahani, Mansoureh A; Ghaffari, Fatemeh; Seyed Fatemi, Naiemeh

2015-01-01

There are widespread misconceptions about the positive effects of opium on coronary artery disease (CAD). Thus, we performed a study to explore the opium addiction process contributing factors among CAD patients using a grounded theory approach. The sample comprised 30 addicted CAD patients and their family members, physicians, nurses and friends. Purposive and theoretical sampling was employed; semi-structured interviews were conducted. Coding and constant comparative analysis techniques were as proposed by Strauss and Corbin (1998). The core category was 'Fighting for Survival', comprising three main themes, namely, 'the gateway', 'blowing into the fire' and 'getting stuck in the mud'. Increasing knowledge about the adverse effects of opium on the cardiovascular system would reinforce prevention and rehabilitation measures. Involving patients' family-members in addiction prevention and rehabilitation programs and referring patients to specialized rehabilitation centres could help patients quit opium. Healthcare providers (HCPs) should notice to the effects of opium consumption among CAD patients; nursing care must be holistic in nature. Although opium is stigmatised in Iran, HCPs must treat addicted CAD patients similar to other patients. Nursing students' must be aware of the negative effects of illegal drugs on CAD patients and the misconceptions regarding the positive effects thereof. Any misconceptions must be probed and clarified. Rehabilitation centres must be supervised by cardiologists and HCPs.
Opium and Afghanistan: Reassessing U.S. Counter-Narcotics Strategy

DTIC Science & Technology

2007-03-30

and effective governance of Afghanistan.”3 This paper examines the nature of the opium problem in Afghanistan and analyzes the current strategy to...Opium is also refined for use in legal prescription painkillers such as OxyContin and Vicodin.14 However, Australia and France currently produce about...is simply inadequate to carry out an effective counter-narcotics campaign. While some regions of Afghanistan are relatively stable and free of

Morphine and Codeine in Oral Fluid after Controlled Poppy Seed Administration

PubMed Central

Concheiro, Marta; Newmeyer, Matthew N.; da Costa, Jose Luiz; Flegel, Ron; Gorelick, David A.; Huestis, Marilyn A.

2014-01-01

Opiates are an important drug class in drug testing programs. Ingestion of poppy seeds containing morphine and codeine can yield positive opiate tests and mislead result interpretation in forensic and clinical settings. Multiple publications evaluated urine opiate concentrations following poppy seed ingestion, but only 2 addressed oral fluid (OF) results; neither provided the ingested morphine and codeine dosage. We administered two 45g raw poppy seed doses, each containing 15.7mg morphine and 3.1mg codeine, 8h apart to 17 healthy adults. All OF specimens were screened by on-site OF immunoassay Draeger DrugTest 5000, and confirmed with OF collected with Oral-Eze® device and quantified by liquid chromatography tandem mass spectrometry (1μg/L morphine and codeine limits of quantification). Specimens (n=459) were collected before and up to 32h after the first dose. All specimens screened positive 0.5h after dosing and remained positive for 0.5-13h at Draeger 20μg/L morphine cutoff. Maximum OF morphine and codeine concentrations (Cmax) were 177 and 32.6μg/L, with times to Cmax (Tmax) of 0.5-1h and 0.5-2.5h post-dose, respectively. Windows of detection after the second dose extended at least 24h for morphine and to 18h for codeine. After both doses, the last morphine positive OF result was 1h with 40μg/L 2004 proposed US Substance Abuse and Mental Health Services Administration cutoff, and 0.5h with 95μg/L cutoff, recently recommended by the Driving Under the Influence of Drugs and Medicines project. Positive OF morphine results are possible 0.5-1h after ingestion of 15.7mg of morphine in raw poppy seeds, depending upon the cutoff employed. PMID:25345619
76 FR 59495 - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

..., Haiti, Honduras, India, Jamaica, Laos, Mexico, Nicaragua, Pakistan, Panama, Peru, and Venezuela. A... provinces, are through Iran to Turkey and Western Europe; through Pakistan to Africa, Asia, and the Middle... of opium poppy cultivated in Pakistan is much less than Afghanistan, the country continues to qualify...
21 CFR 1304.31 - Reports from manufacturers importing narcotic raw material.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reports from manufacturers importing narcotic raw... RECORDS AND REPORTS OF REGISTRANTS Reports § 1304.31 Reports from manufacturers importing narcotic raw material. (a) Every manufacturer which imports or manufactures from narcotic raw material (opium, poppy...
21 CFR 1304.31 - Reports from manufacturers importing narcotic raw material.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Reports from manufacturers importing narcotic raw... RECORDS AND REPORTS OF REGISTRANTS Reports § 1304.31 Reports from manufacturers importing narcotic raw material. (a) Every manufacturer which imports or manufactures from narcotic raw material (opium, poppy...
75 FR 32505 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

... 55858), Johnson Matthey, Inc., Pharmaceutical Materials, 2003 Nolte Drive, West Deptford, New Jersey... Phenylacetone (8501) II Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668) II Poppy Straw Concentrate (9670) II The company plans to import the listed controlled substances as raw...
The medieval Persian manuscript of Afyunieh: the first individual treatise on the opium and addiction in history.

PubMed

Moosavyzadeh, Abdolali; Ghaffari, Farzaneh; Mosavat, Seyed Hamdollah; Zargaran, Arman; Mokri, Azarakhsh; Faghihzadeh, Soghrat; Naseri, Mohsen

2018-03-01

According to historical evidence, the abuse of opium has been reported all over the globe-specifically throughout Eastern nations-since the sixteenth century. Before that, opium had mostly been applied as medication. Reference has been made in traditional Persian medical literature to the method of cultivation, properties, side effects and toxicity. In sixteenth century Iran, during the reign of the Safavids, opium abuse began. It was from then that prominent Persian scholars started to think of solutions to this societal problem. One of the most famous scholars was Imad al-Din Mahmud ibn Mas'ud Shirazi, who composed a book concerning addiction-Afyunieh, a comprehensive book on the topic of opium and all issues of opium. Furthermore, he recommended methods for reducing opium dose as well as substitution with other medications that had a narrower range of side effects, in order to eradicate dependency upon opium and opium-derived materials. This is most likely the first book that comprehensively addressed opium and discussed drug rehabilitation methodology, in traditional Persian medical literature. In this historical review, the authors have introduced the book Afyunieh, which presents methods for treating addiction to and giving up opium; the text comprises a synthesis of the author's opinions, professional experience and references to the work of other famous physicians. Copyright © 2018 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.
The pro-heroin effects of anti-opium laws in Asia.

PubMed

Westermeyer, J

1976-09-01

Over 25 years anti-opium laws were enacted by three Asian governments in countries where opium use was traditional. Within months, heroin use suddenly appeared; and within a decade, heroin addiction surpassed opium addiction. The laws led to (1) increased price of narcotic drugs, (2) a heroin "industry," (3) corruption of the law enforcement system, and (4) major health problems involving parenteral drug use. The Asian experience indicates that antinarcotic laws can be effective only with careful preparations: (1) changing society's attitude toward the traditional drug from ambivalence to opposition; (2) mobilizing resources to treat and rehabilitate all addicts within a short period of time; (3) developing the social will to incarcerate all "recidivist" addicts for a prolonged period; and (4) preventing narcotic production or importation.
Changes in serum biochemical factors associated with opium addiction after addiction desertion.

PubMed

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients.
Lead poisoning outbreak among opium users in the Islamic Republic of Iran, 2016–2017

PubMed Central

Ghane, Talat; Zamani, Nasim; Beyrami, Ali; Noroozi, Alireza

2018-01-01

Abstract Objective To describe an outbreak of lead poisoning among opium users in the Islamic Republic of Iran and estimate the number of affected people in the country. Methods We used data from the country’s largest poison treatment centre to illustrate the epidemiology of an outbreak of lead poisoning in oral opium users. We describe the government’s referral and treatment guidelines in response to the outbreak. Based on the number of individuals treated and previous studies on the prevalence of oral opium use we estimated the total number of people at risk of lead-contaminated opium nationwide. Findings In February 2016, we noticed a steep increase in the numbers of oral opium users referred to our poison treatment centre with abdominal pain, anaemia and constipation. Numbers peaked in June 2016 but the outbreak was ongoing in August 2017. The mean blood lead level in a sample of 80 patients was 140.3 µg/dL (standard deviation: 122.6). Analysis of an illegal opium sample showed 3.55 mg lead in 1 g opium. Treatment was exposure reduction with opioid substitutes and laxatives, or chelation therapy if indicated. Over 7 months, 4294 poison cases were seen at main referral hospitals in Tehran out of an estimated 31 914 oral opium users in the city. We estimate more than 260 000 out of 773 800 users nationwide remain untreated and at risk of poisoning. Conclusion Lead-contaminated opium and heroin that has transited through the Iranian markets is a global risk and highlights a need for better monitoring of illegal drug supplies. PMID:29531415
77 FR 5846 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... import narcotic raw material are not appropriate, in accordance with 72 FR 3417 (2007). DEA has... basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Opium, raw (9600) II Poppy... to use it as a base material in the bulk manufacture of another controlled substance. No comments or...
Changes in Serum Biochemical Factors Associated with Opium Addiction after Addiction Desertion

PubMed Central

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

Background The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. Methods In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. Findings According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. Conclusion According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients. PMID:25984281
77 FR 43862 - Importer of Controlled Substances; Notice of Registration; Noramco, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-26

... basic classes of controlled substances: Drug Schedule Phenylacetone (8501) II Opium, raw (9600) II Poppy... a controlled substance. Comments and requests for hearings on applications to import narcotic raw material are not appropriate. 72 FR 3417 (2007). DEA has considered the factors in 21 U.S.C. 823(a) and 952...
76 FR 35241 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

...-Piperidine (8333).. II Phenylacetone (8501) II Raw Opium (9600) II Concentrate of Poppy Straw (9670) II The... Technologies, 72 FR 3417 (2007), comments and requests for hearings on applications to import narcotic raw material are not appropriate. Any bulk manufacturer who is presently, or is applying to be, registered with...
77 FR 43861 - Importer of Controlled Substances; Notice Of Application; Cody Laboratories, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-26

... basic class of any controlled substance in schedule I or II are, and will continue to be, required to... importer of the following basic classes of controlled substances: Drug Schedule Opium, Raw (9600) II Concentrate Poppy Straw (9670) II Tapentadol (9780) II The company plans to import narcotic raw materials for...
Poppy Seed Consumption or Opiate Use: The Determination of Thebaine and Opiates of Abuse in Postmortem Fluids and Tissues

DTIC Science & Technology

2005-06-01

codeine, following the consumption of poppy seeds .4-8 Scientific literature has clearly demonstrated the distinct possibil- ity of a morphine and/or...poppy seeds and is only present following heroin use.5 Therefore, 6-MAM is considered a heroin- specific catabolite and is legally defensible
1H NMR-based metabolic profiling for evaluating poppy seed rancidity and brewing.

PubMed

Jawień, Ewa; Ząbek, Adam; Deja, Stanisław; Łukaszewicz, Marcin; Młynarz, Piotr

2015-12-01

Poppy seeds are widely used in household and commercial confectionery. The aim of this study was to demonstrate the application of metabolic profiling for industrial monitoring of the molecular changes which occur during minced poppy seed rancidity and brewing processes performed on raw seeds. Both forms of poppy seeds were obtained from a confectionery company. Proton nuclear magnetic resonance (1H NMR) was applied as the analytical method of choice together with multivariate statistical data analysis. Metabolic fingerprinting was applied as a bioprocess control tool to monitor rancidity with the trajectory of change and brewing progressions. Low molecular weight compounds were found to be statistically significant biomarkers of these bioprocesses. Changes in concentrations of chemical compounds were explained relative to the biochemical processes and external conditions. The obtained results provide valuable and comprehensive information to gain a better understanding of the biology of rancidity and brewing processes, while demonstrating the potential for applying NMR spectroscopy combined with multivariate data analysis tools for quality control in food industries involved in the processing of oilseeds. This precious and versatile information gives a better understanding of the biology of these processes.
Analysis of volatile compounds and triglycerides of seed oils extracted from different poppy varieties (Papaver somniferum L.).

PubMed

Krist, Sabine; Stuebiger, Gerald; Unterweger, Heidrun; Bandion, Franz; Buchbauer, Gerhard

2005-10-19

Poppy seed oil (Oleum Papaveris Seminis) is used for culinary and pharmaceutical purposes, as well as for making soaps, paints, and varnishes. Astonishingly, hardly anything was yet known about the volatile compounds of this promising comestible. Likewise, there are no current published data about the triglyceride (TAG) composition of poppy seed oils available. In this investigation solid-phase microextraction (SPME) with DVB/Carboxen/PDMS Stable-Flex fiber was applied to the study of volatile compounds of several seed oil samples from Papaver somniferum L. (Papaveraceae). 1-Pentanol (3.3-4.9%), 1-hexanal (10.9-30.9%), 1-hexanol (5.3-33.7%), 2-pentylfuran (7.2-10.0%), and caproic acid (2.9-11.5%) could be identified as the main volatile compounds in all examined poppy seed oil samples. Furthermore, the TAG composition of these oils was analyzed by MALDI-ReTOF- and ESI-IT-MS/MS. The predominant TAG components were found to be composed of linoleic, oleic, and palmitic acid, comprising approximately 70% of the oils. TAG patterns of the different poppy varieties were found to be very homogeneous, showing also no significant differences in terms of the applied pressing method of the plant seeds.
Randomized controlled trial of postoperative belladonna and opium rectal suppositories in vaginal surgery.

PubMed

Butler, Kristina; Yi, John; Wasson, Megan; Klauschie, Jennifer; Ryan, Debra; Hentz, Joseph; Cornella, Jeffrey; Magtibay, Paul; Kho, Roseanne

2017-05-01

After vaginal surgery, oral and parenteral narcotics are used commonly for pain relief, and their use may exacerbate the incidence of sedation, nausea, and vomiting, which ultimately delays convalescence. Previous studies have demonstrated that rectal analgesia after surgery results in lower pain scores and less intravenous morphine consumption. Belladonna and opium rectal suppositories may be used to relieve pain and minimize side effects; however, their efficacy has not been confirmed. We aimed to evaluate the use of belladonna and opium suppositories for pain reduction in vaginal surgery. A prospective, randomized, double-blind, placebo-controlled trial that used belladonna and opium suppositories after inpatient or outpatient vaginal surgery was conducted. Vaginal surgery was defined as (1) vaginal hysterectomy with uterosacral ligament suspension or (2) posthysterectomy prolapse repair that included uterosacral ligament suspension and/or colporrhaphy. Belladonna and opium 16A (16.2/60 mg) or placebo suppositories were administered rectally immediately after surgery and every 8 hours for a total of 3 doses. Patient-reported pain data were collected with the use of a visual analog scale (at 2, 4, 12, and 20 hours postoperatively. Opiate use was measured and converted into parenteral morphine equivalents. The primary outcome was pain, and secondary outcomes included pain medication, antiemetic medication, and a quality of recovery questionnaire. Adverse effects were surveyed at 24 hours and 7 days. Concomitant procedures for urinary incontinence or pelvic organ prolapse did not preclude enrollment. Ninety women were randomly assigned consecutively at a single institution under the care of a fellowship-trained surgeon group. Demographics did not differ among the groups with mean age of 55 years, procedure time of 97 minutes, and prolapse at 51%. Postoperative pain scores were equivalent among both groups at each time interval. The belladonna and opium group used a
Historical trends in the production and consumption of illicit drugs in Mexico: implications for the prevention of blood borne infections.

PubMed

Bucardo, Jesus; Brouwer, Kimberly C; Magis-Rodríguez, Carlos; Ramos, Rebeca; Fraga, Miguel; Perez, Saida G; Patterson, Thomas L; Strathdee, Steffanie A

2005-09-01

Mexico has cultivated opium poppy since before the 1900's and has been an important transit route for South American cocaine for decades. However, only recently has drug use, particularly injection drug use, been documented as an important problem. Heroin is the most common drug used by Mexican injection drug users (IDUs). Increased cultivation of opium poppy in some Mexican states, lower prices for black tar heroin and increased security at U.S.-Mexican border crossings may be contributing factors to heroin use, especially in border cities. Risky practices among IDUs, including needle sharing and shooting gallery attendance are common, whereas perceived risk for acquiring blood borne infections is low. Although reported AIDS cases attributed to IDU in Mexico have been low, data from sentinel populations, such as pregnant women in the Mexican-U.S. border city of Tijuana, suggest an increase in HIV prevalence associated with drug use. Given widespread risk behaviors and rising numbers of blood borne infections among IDUs in Mexican-U.S. border cities, there is an urgent need for increased disease surveillance and culturally appropriate interventions to prevent potential epidemics of blood borne infections. We review available literature on the history of opium production in Mexico, recent trends in drug use and its implications, and the Mexican response, with special emphasis on the border cities of Ciudad Juarez and Tijuana.
Historical trends in the production and consumption of illicit drugs in Mexico: Implications for the prevention of blood borne infections

PubMed Central

Bucardo, Jesus; Brouwer, Kimberly C.; Magis-Rodríguez, Carlos; Ramos, Rebeca; Fraga, Miguel; Perez, Saida G.; Patterson, Thomas L.; Strathdee, Steffanie A.

2007-01-01

Mexico has cultivated opium poppy since before the 1900’s and has been an important transit route for South American cocaine for decades. However, only recently has drug use, particularly injection drug use, been documented as an important problem. Heroin is the most common drug used by Mexican injection drug users (IDUs). Increased cultivation of opium poppy in some Mexican states, lower prices for black tar heroin and increased security at U.S.-Mexican border crossings may be contributing factors to heroin use, especially in border cities. Risky practices among IDUs, including needle sharing and shooting gallery attendance are common, whereas perceived risk for acquiring blood borne infections is low. Although reported AIDS cases attributed to IDU in Mexico have been low, data from sentinel populations, such as pregnant women in the Mexican-U.S. border city of Tijuana, suggest an increase in HIV prevalence associated with drug use. Given widespread risk behaviors and rising numbers of blood borne infections among IDUs in Mexican-U.S. border cities, there is an urgent need for increased disease surveillance and culturally appropriate interventions to prevent potential epidemics of blood borne infections. We review available literature on the history of opium production in Mexico, recent trends in drug use and its implications, and the Mexican response, with special emphasis on the border cities of Ciudad Juarez and Tijuana. PMID:16102372

The Paradoxical and Unintended Effects of the War on Drugs

DTIC Science & Technology

1993-04-01

of coca leaves; 2) heroin, derived from the opium poppy; and, 3) marijuana and hashish from the cannabis plant. Cocaine and crack come into the U.S...example, is 28 to 43 per cent of its total exports, and generates more money than its major export, coffee . 52 Moreover, the drug business is a major source
Did J. Marion Sims deliberately addict his first fistula patients to opium?

PubMed

Wall, L Lewis

2007-07-01

American surgeon J. Marion Sims (1813-83) is regarded by many modern authors as a controversial figure because he carried out a series of experimental surgeries on enslaved African American women between 1846 and 1849 in an attempt to cure them of vesicovaginal fistulas, which they had all developed as a result of prolonged obstructed labor. He operated on one woman, Anarcha Westcott, thirty times before he successfully closed her fistula. Sims performed these fistula repair operations without benefit of anesthesia but gave these women substantial doses of opium afterwards. Several modern writers have alleged that Sims did this in order to addict them to the drug and thereby to enhance his control over them. This article examines the controversy surrounding Sims' use of postoperative opium in these enslaved surgical patients. The evidence suggests that although these women were probably tolerant to the doses of opium that he used, there is no evidence that he deliberately tried to addict them to this drug. Sims' use of postoperative opium appears to have been well supported by the therapeutic practices of his day, and the regimen that he used was enthusiastically supported by many contemporary surgeons.
Clipping affects flowering of California poppy at two growth stages

Treesearch

Raymond D. Ratliff; Richard L. Hubbard

1975-01-01

The effects of clipping California-poppy (Eschscholzia californica Cham.) at various growth stages on plant survival, flowering, herbage yield, and root production were studied at the San Joaquin Experimental Range, in central California. Plants were clipped once to a 2-cm stubble at one of six stages. Through the early reproductive stage, a single...
Pharmacological therapies for management of opium withdrawal.

PubMed

Rahimi-Movaghar, Afarin; Gholami, Jaleh; Amato, Laura; Hoseinie, Leila; Yousefi-Nooraie, Reza; Amin-Esmaeili, Masoumeh

2018-06-21

Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. We used the standard methodological procedures expected by Cochrane. We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1
Urinary excretion study following consumption of various poppy seed products and investigation of the new potential street heroin marker ATM4G.

PubMed

Maas, Alexandra; Krämer, Michael; Sydow, Konrad; Chen, Pai-Shan; Dame, Torsten; Musshoff, Frank; Diehl, Bernd W K; Madea, Burkhard; Hess, Cornelius

2017-03-01

Discrimination between street heroin consumption and poppy seed ingestion represents a major toxicological challenge in daily routine work. Several difficulties associated with conventional street heroin markers originate from their versatile occurrence in various poppy seed products and medications, respectively, as well as to small windows of detection. A novel opportunity to overcome these hindrances is represented by the new potential street heroin marker acetylated-thebaine-4-metabolite glucuronide (ATM4G), originating from thebaine during street heroin synthesis followed by metabolic reactions after administration. In this study, urine samples after consumption of different German poppy seed products and urine samples from subjects with suspicion of preceding heroin consumption were tested for ATM4G, 6-AC (6-acetylcodeine), papaverine, noscapine, 6-MAM (6-monoacetylmorphine), morphine, and codeine. Neither 6-AC and 6-MAM nor ATM4G but morphine and codeine could be detected in urine samples following poppy seed ingestion. As well, neither papaverine nor noscapine could be observed even after consumption of poppy seeds containing up to 37 µg noscapine and up to 9.8 µg papaverine, respectively. Concerning the urine samples with suspicion of preceding heroin consumption, ATM4G could be detected in 9 of 43 cases. By contrast, evidence of 6-AC and 6-MAM, respectively, could only be seen in 7 urine samples. In conclusion, ATM4G should be measured additionally in cases requiring discrimination of street heroin consumption from poppy seed intake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Do Consumers Substitute Opium for Hashish? An Economic Analysis of Simultaneous Cannabinoid and Opiate Consumption in a Legal Regime

PubMed Central

Chandra, Madhur

2015-01-01

Aim To analyze interrelationships in the consumption of opiates and cannabinoids in a legal regime and, specifically, whether consumers of opiates and cannabinoids treat them as substitutes for each other. Method Econometric dynamic panel data models for opium consumption are estimated using the generalized method of moments (GMM). A unique dataset containing information about opiate (opium) consumption from the Punjab province of British India for the years 1907–1918 is analyzed (n=272) as a function of its own price, the prices of two forms of cannabis (the leaf (bhang), and the resin (charas, or hashish)), and wage income. Cross-price elasticities are examined to reveal substitution or complementarity between opium and cannabis. Results Opium is a substitute for charas (or hashish), with a cross price elasticity (β3) of 0.14 (p < 0.05), but not for bhang (cannabis leaves; cross price elasticity = 0.00, p > 0.10). Opium consumption (β1 = 0.47 to 0.49, p < 0.01) shows properties of habit persistence consistent with addiction. The consumption of opium is slightly responsive (inelastic) to changes in its own price (β2 = −0.34 to −0.35, p < 0.05 to 0.01) and consumer wages (β4 = 0.15, p < 0.05). Conclusion Opium and hashish, a form of cannabis, are substitutes. In addition, opium consumption displays properties of habit persistence and slight price and wage income responsiveness (inelasticity) consistent with an addictive substance. PMID:26455552
Do consumers substitute opium for hashish? An economic analysis of simultaneous cannabinoid and opiate consumption in a legal regime.

PubMed

Chandra, Siddharth; Chandra, Madhur

2015-11-01

To analyze interrelationships in the consumption of opiates and cannabinoids in a legal regime and, specifically, whether consumers of opiates and cannabinoids treat them as substitutes for each other. Econometric dynamic panel data models for opium consumption are estimated using the generalized method of moments (GMM). A unique dataset containing information about opiate (opium) consumption from the Punjab province of British India for the years 1907-1918 is analyzed (n=252) as a function of its own price, the prices of two forms of cannabis (the leaf (bhang), and the resin (charas, or hashish)), and wage income. Cross-price elasticities are examined to reveal substitution or complementarity between opium and cannabis. Opium is a substitute for charas (or hashish), with a cross price elasticity (βˆ3) of 0.14 (p<0.05), but not for bhang (cannabis leaves; cross price elasticity=0.00, p>0.10). Opium consumption (βˆ1=0.47 to 0.49, p<0.01) shows properties of habit persistence consistent with addiction. The consumption of opium is slightly responsive (inelastic) to changes in its own price (βˆ2=-0.34 to -0.35, p<0.05 to 0.01) and consumer wages (βˆ1=0.15, p<0.05). Opium and hashish, a form of cannabis, are substitutes. In addition, opium consumption displays properties of habit persistence and slight price and wage income responsiveness (inelasticity) consistent with an addictive substance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.

PubMed

Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; LoDico, Charles; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

2014-08-01

Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45 g oral poppy seed doses 8 h apart, each containing 15.7 mg morphine and 3mg codeine. Urine was collected ad libitum up to 32 h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2000 and 300 μg/L cutoffs, and the ThermoFisher CEDIA(®) heroin metabolite (6-acetylmorphine, 6-AM) and Lin-Zhi 6-AM immunoassays with 10 μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32 h following dosing; 26.6% and 83.4% were positive for morphine at 2000 and 300 μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7522 μg/L with a median peak concentration of 5239 μg/L. The median first morphine-positive urine sample at 2000 μg/L cutoff concentration occurred at 6.6 h (1.2-12.1), with the last positive from 2.6 to 18 h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2000 μg/L, but 20.2% exceeded 300 μg/L, with peak concentrations of 658 μg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300 μg/L cutoffs. The CEDIA 6-AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. Copyright
Morphine and Codeine Concentrations in Human Urine following Controlled Poppy Seeds Administration of Known Opiate Content

PubMed Central

Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; LoDico, Charles; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

2014-01-01

Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45g oral poppy seed doses 8h apart, each containing 15.7mg morphine and 3mg codeine. Urine was collected ad libitum up to 32h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2,000 and 300μg/L cutoffs, and the ThermoFisher CEDIA® Heroin Metabolite (6-acetylmorphine, 6AM) and Lin-Zhi 6AM immunoassays with 10μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32h following dosing; 26.6% and 83.4% were positive for morphine at 2,000 and 300μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7,522μg/L with a median peak concentration of 5,239μg/L. The median first morphine-positive urine sample at 2,000μg/L cutoff concentration occurred at 6.6h (1.2-12.1), with the last positive from 2.6 to 18h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2,000μg/L, but 20.2% exceeded 300μg/L, with peak concentrations of 658 μg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300μg/L cutoffs. The CEDIA 6AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID:24887324
Parenteral poppy seed tea packs a powerful punch.

PubMed

Monaghan, Dominic; Peckler, Brad

2013-12-13

Poppy seed tea (PST) has a long history of use for its medicinal (analgesic, anti-diarrhoeal, anxiolytic) effects. It is also commonly used as a recreational drug in its oral form throughout the world, but reports of intravenous use are very rare. We present two cases of intravenously injected PST with dramatic effects in order to create awareness among health professionals of this method of drug use and its potential complications, as well as to help clinicians dealing with opiate-dependent patients to warn them of the risk.
Quadriplegia due to lead-contaminated opium--case report.

PubMed

Beigmohammadi, Mohammad Taghi; Aghdashi, Moosa; Najafi, Atabak; Mojtahedzadeh, Mojtaba; Karvandian, Kassra

2008-10-01

Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia. Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic. The delayed treatment of lead poisoning may lead to irreversible motor neuron defect.
Oral opium: an unusual cause of lead poisoning.

PubMed

Meybodi, Farid Aghaee; Eslick, Guy D; Sasani, Sanaz; Abdolhoseyni, Mohammad; Sazegar, Sasan; Ebrahimi, Farzaneh

2012-06-01

The number of cases of lead poisoning (LP), a widely known disease with various aetiologies, being reported globally has decreased over the years due to both limited domestic applications of lead and enforcement of stringent safety measures. However, a new presentation of lead poisoning, lead-contaminated opium (LCO), is gradually emerging in our region. This study aimed to determine the prevalence and clinical effects of lead toxicity associated with opium use. Between November 2006 and December 2007, all patients diagnosed with LP at a central laboratory in Tehran, Iran, were assessed for potential causes of poisoning. Patients with a history of LCO abuse were evaluated and recruited for the study. Overall, there were 240 patients with LP, and poisoning from LCO was diagnosed in 25 patients. The duration of addiction was between three months and 40 years, and the duration of symptoms was 28.1 ± 17.7 days. Mean blood lead levels of the patients were 145 ± 61 (range 61-323) μg/dL. The average creatinine and haemoglobin levels were 77.4 ± 8.1 μmol/L and 105 ± 25 g/L, respectively. The association between the duration of addiction and levels of lead in blood was not statistically significant (r = -0.142, p = 0.54). The most common symptoms were gastrointestinal complaints, followed by musculoskeletal complaints with muscle weakness (92%). Anorexia was also a leading complaint. The results of our study suggest that the possibility of LP should be considered with high suspicion among opium users presenting with acute abdominal symptoms.
Translations on Narcotics and Dangerous Drug No. 289.

DTIC Science & Technology

1977-03-16

Traffickers Arrested With Marihuana , Heroin (DIARIO DE NOGALES, 4 Feb 77) 43 Drugs and Traffickers Captured (DIARIO DE NOGALES, 4 Feb 77) 44...Guadalajara: Psychotropics and Medicine Samples Sold 51 NEAR EAST AND AFRICA IRAN Briefs Sabzevar Opium Haul 52 CONTENTS (Continued) Page...had cultivated poppies were growing coffee, vegetables, legumes, fruits as well as medicinal plants in the highlands," Dr de Beus recounted to
The california poppy (eschscholtzia mexicana) as a copper indicator plant - a new example

USGS Publications Warehouse

Chaffee, M.A.; Gale, C.W.

1976-01-01

The abundance and distribution of the California poppy (Eschscholtzia mexicana) correlates closely with the copper-rich outcrop of a small porphyry-type deposit in Arizona. Chemical factors are probably more important than physical factors in determining why this species is sometimes found as a copper indicator plant. ?? 1976.
Organic parasite control for poultry and rabbits in British Columbia, Canada

PubMed Central

2011-01-01

Plants used for treating endo- and ectoparasites of rabbits and poultry in British Columbia included Arctium lappa (burdock), Artemisia sp. (wormwood), Chenopodium album (lambsquarters) and C. ambrosioides (epazote), Cirsium arvense (Canada thistle), Juniperus spp. (juniper), Mentha piperita (peppermint), Nicotiana sp. (tobacco), Papaver somniferum (opium poppy), Rubus spp. (blackberry and raspberry relatives), Symphytum officinale (comfrey), Taraxacum officinale (common dandelion), Thuja plicata (western redcedar) and Urtica dioica (stinging nettle). PMID:21756341
Counterinsurgency in Afghanistan, Rand Counterinsurgency Study, Volume 4

DTIC Science & Technology

2008-01-01

population. These forces may be badly financed and equipped, orga- nizationally inept, corrupt, politically divided, and poorly informed about events...dominated by drug traffick- ers, the opium poppy economy financed a mode of local government that undermined the power of the central government.29...salaries are financed by non-believers. Unless you stop getting wages from them, you will be counted among the Ameri- can puppets.”45 This rationale
Hmong women, opium cultivation and livestock production in Lao PDR.

PubMed

Oparaocha, S

1998-01-01

This article analyzes the effects on Hmong women of a Laotian government policy to replace production of opium by upland farmers with other cash crops by the year 2000. In 1996, 15% of the population relied on opium as a cash crop. This project aimed to include Hmong women in small livestock production in 2 villages: Ban Kampanien and Ban Pha Ven in Nong Het district, Xieng Khouang province, near the Vietnamese border. Interviews were conducted among 33 families using the Harvard Gender Analytical Tools (1991) to determine gender roles in livestock production. Participatory assessment relied on matrix ranking, resource maps, and trend charts. In Nong Het, White Hmong dominate. Average family size is 7 persons. Polygamy is allowed, but declining. The birthrate is high. Swidden agriculture is practiced. Agricultural production meets demand. Patriarchal authority dominates; men and women have separate public and private spheres. Education favors boys. Women are involved in all aspects of agricultural production. The author describes women's role in small livestock production and gender roles in feed management. Women exercise autonomy only through raising livestock and poultry. Women's production is constrained by limited access to extension services, feed resources, labor saving technology, and credit. In order to offset the loss of income from opium, Hmong women need to increase their income by increasing the product output per animal using selective breeding, and decreasing time spent on preparing and processing food. Assistance should be provided to improve women's resources and knowledge.
Unraveling Additional O-Methylation Steps in Benzylisoquinoline Alkaloid Biosynthesis in California Poppy (Eschscholzia californica).

PubMed

Purwanto, Ratmoyo; Hori, Kentaro; Yamada, Yasuyuki; Sato, Fumihiko

2017-09-01

California poppy (Eschscholzia californica), a member of the Papaveraceae family, produces many biologically active benzylisoquinoline alkaloids (BIAs), such as sanguinarine, macarpine and chelerythrine. Sanguinarine biosynthesis has been elucidated at the molecular level, and its biosynthetic genes have been isolated and used in synthetic biology approaches to produce BIAs in vitro. However, several genes involved in the biosynthesis of macarpine and chelerythrine have not yet been characterized. In this study, we report the isolation and characterization of a novel O-methyltransferase (OMT) involved in the biosynthesis of partially characterized BIAs, especially chelerythrine. A search of the RNA sequence database from NCBI and PhytoMetaSyn for the conserved OMT domain identified 68 new OMT-like sequences, of which the longest 22 sequences were selected based on sequence similarity. Based on their expression in cell lines with different macarpine/chelerythrine profiles, we selected three OMTs (G2, G3 and G11) for further characterization. G3 expression in Escherichia coli indicated O-methylation activity of the simple benzylisoquinolines, including reticuline and norreticuline, and the protoberberine scoulerine with dual regio-reactivities. G3 produced 7-O-methylated, 3'-O-methylated and dual O-methylated products from reticuline and norreticuline, and 9-O-methylated tetrahydrocolumbamine, 2-O-methylscoulerine and tetrahydropalmatine from scoulerine. Further enzymatic analyses suggested that G3 is a scoulerine-9-O-methyltransferase for the biosynthesis of chelerythrine in California poppy. In the present study, we discuss the physiological role of G3 in BIA biosynthesis. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Opium -- The Fuel of Instability in Afghanistan: Why the Military Must be Involved in the Solution, and Recommendations for Action

DTIC Science & Technology

2007-04-18

believed insurgencies in the 1950’s and 60’s “became factors for advancing export of opium from the zone [mountainous region of Thailand adjacent to China ...production and sales of opium.” “This [the Revolutionary Armed Forces of Columbia’s] power is overwhelmingly supported by cocaine and opium sales from...2006. 43Ed Blanche, “Multibillion $ Illicit Drug Sales Fuel Terror Offensive,” The Middle East (November 2004): 10. 44Faisal Islam, “World Bank Chief
No association between GSTM1 and GSTT1 genetic polymorphisms and susceptibility to opium sap dependence.

PubMed

Saify, Khyber; Khalighinasab, Mohammad Rashid; Saadat, Mostafa

2016-03-01

Glutathione S-transferases (GSTs; EC: 2.5.1.18) are a ubiquitous family of eukaryotic and prokaryotic phase II metabolic isozymes. Genes encoding GSTM1 (OMIM: 138350), and GSTT1 (OMIM: 600436) are members of class mu and theta, respectively. The most common polymorphism in the GSTM1 is a deletion of the whole GSTM1 gene with a lack of enzyme activity. A homozygous deletion in the GSTT1 has also been reported (null genotypes of GSTT1). The aim of the present study was to investigate the association between GSTM1 and GSTT1 polymorphisms and risk of dependency to opium sap. The present study was performed in Shiraz (southern Iran). In total, 71 males dependent to opium sap and 590 healthy males (as a control group) were included in this study. The genotypes of GSTM1 and GSTT1 polymorphisms were determined by PCR. Our data indicate that neither GSTM1 (OR=0.78, 95% CI: 0.47-1.27, P=0.325) nor GSTT1 (OR=1.25, 95% CI: 0.70-2.21, P=0.442) null genotypes significantly associated with the risk of opium sap dependence. There is no additive effect of the null genotypes of GSTT1 and GSTM1 in relation to the risk of dependency to opium sap. The present study indicated that the null genotypes of GSTT1 and GSTM1 are not risk factor for opium sap dependence.

Rapid qualitative and quantitative analysis of opiates in extract of poppy head via FTIR and chemometrics: towards in-field sensors.

PubMed

Turner, Nicholas W; Cauchi, Michael; Piletska, Elena V; Preston, Christopher; Piletsky, Sergey A

2009-07-15

Identification and quantification of the opiates morphine and thebaine has been achieved in three commercial poppy cultivars using FTIR-ATR spectroscopy, from a simple and rapid methanolic extraction, suitable for field analysis. The limits of detection were 0.13 mg/ml (0.013%, w/v) and 0.3 mg/ml (0.03%, w/v) respectively. The concentrations of opiates present were verified with HPLC-MS. The chemometrics has been used to identify specific "signature" peaks in the poppy IR spectra for characterisation of cultivar by its unique fingerprint offering a potential forensic application in opiate crop analysis.
Effects of clonidine premedication upon postoperative shivering and recovery time in patients with and without opium addiction after elective leg fracture surgeries.

PubMed

Jabbary Moghaddam, Morteza; Ommi, Davood; Mirkheshti, Alireza; Dabbagh, Ali; Memary, Elham; Sadeghi, Afsaneh; Yaseri, Mehdi

2013-01-01

Opium is a highly addictive agent and the most common narcotic often misused in Iran. The pharmacokinetic of anesthetic drugs in patients with opium addiction is one of the great challenges for anesthesiologists. Hemodynamic instability and postoperative side effects are of these challenges which should be managed correctly. In this study we aimed to assess the effects of clonidine upon post anesthesia shivering and recovery time in patients with and without opium addiction after general anesthesia to decrease the subsequent complications related to the shivering and elongation of recovery time. In a randomized clinical trial, 160 patients candidates for elective leg fracture operations under general anesthesia were studied in four groups of 40 patients: Group 1 (placebo 1) were patients without addiction who got placebo 90 minutes before the operation. Group 2 (placebo 2) were patients with opium addiction which received placebo as group 1. Group 3 (Clonidine 1) patients without addiction who got clonidine 90 minutes before the operation and group 4 (Clonidine 2) who were opium addicted ones which received clonidine as premedication. None of the patients with and without addiction in clonidine groups had shivering after the operation but in placebo groups shivering was observed and the difference between clonidine and placebo groups was statistically significant (P < 0.01). Recovery time in clonidine groups of patients with and without addiction was less than placebo ones (both P < 0.01) which the magnitude of difference was higher in opium addicted than non-addicted patients (P = 0.04). Premedication with clonidine in patients with and without opium addiction can be effective to decrease the incidence of shivering and recovery time after operation.
'Poppy seeds' in stomach aspirates: is oral omeprazole extemporaneous dispersion bioavailable?

PubMed

Tuleu, Catherine; Arenas-Lopez, Sara; Robinson, Chris; McCarthy, David; Paget, Richard I J; Tibby, Shane; Taylor, Kevin M G

2008-07-01

We report the appearance of 'poppy seed'-like structures found in the aspirated stomach contents and faeces of a 3-month-old infant receiving an omeprazole liquid via nasogastric tube, prepared by dispersing an omeprazole tablet (10 mg MUPS(R)) in water. Electron microscopy and mass spectroscopy indicated that these particles were hollow, dark purple coloured spheres comprising undissolved omeprazole and its degradation products. These observations suggest rapid degradation of omeprazole in the acid stomach contents, with compromised absorption of active drug. Consequently, dispersion of omeprazole in water may be an inappropriate formulation in this setting.
Effects of opium consumption on coronary artery disease risk factors and oral health: Results of Kerman Coronary Artery Disease Risk factors Study a population-based survey on 5900 subjects aged 15-75 years.

PubMed

Najafipour, Hamid; Masoomi, Mohammad; Shahesmaeili, Armita; Haghdoost, Ali Akbar; Afshari, Mahdi; Nasri, Hamid Reza; Kahnooji, Masoomeh; Samadi, Sadra; Mirzazadeh, Ali

2015-01-01

Opium abuse as a relatively common behavior among Iranian population may have an association with the other coronary artery disease (CAD) risk factors. Here, we reported the prevalence of opium abuse and its co-exposures with oral health and other CAD risk factors. We recruited 5900 inhabitant aged 15-75 years using a randomized cluster household survey. All were interviewed for level of physical activity (PA), depression, anxiety and opium use and assessed for hypertension, diabetes, hyperlipidemia, and oral health status. Regarding to opium abuse, participants were grouped into: "Non-," "occasional," and "dependent" users. Using logistic regression model for every CAD risk factor, we assessed whether the co-exposure of opium and CAD risk factor is significant. Overall, 10.6% reported ever opium use including 5.6% dependent and 5% occasional users. The prevalence of opium abuse was increased from 2.1% in 15-25 years to 24.5% in 55-64 years group. Opium abuse, in occasional and dependent forms, was associated with depression (adjusted odds ratio [AOR] 1.81 and 2.49) and low PS (AOR 1.43 and 1.71 respectively). Dependents were less obese than nonusers (P < 0.01). Opium abuse had no significant association with hypertension, diabetes, oral health status and lipid profile. Opium abuse was associated with depression and low PA. No ameliorative effect was observed on hypertension, diabetes, and plasma lipid profile. Therefore, positive association of opium with depression and LPA and the incorrectness of belief on its ameliorative effect on three other important risk factors of CAD should be clearly highlighted in public health messages to the community.
Coca and poppy eradication in Colombia: environmental and human health assessment of aerially applied glyphosate.

PubMed

Solomon, Keith R; Anadón, Arturo; Carrasquilla, Gabriel; Cerdeira, Antonio L; Marshall, Jon; Sanin, Luz-Helena

2007-01-01

The production of coca and poppy as well as the processing and production of cocaine and heroin involve significant environmental impacts. Both coca and poppy are grown intensively in a process that involves the clearing of land in remote areas, the planting of the crop, and protection against pests such as weeds, insects, and pathogens. The aerial spray program to control coca and poppy production in Colombia with the herbicide glyphosate is conducted with modern state-of-the-art aircraft and spray equipment. As a result of the use of best available spray and navigation technology, the likelihood of accidental off-target spraying is small and is estimated to be less than 1% of the total area sprayed. Estimated exposures in humans resulting from direct overspray, contact with treated foliage after reentry to fields, inhalation, diet, and drinking water were small and infrequent. Analyses of surface waters in five watersheds showed that, on most occasions, glyphosate was not present at measurable concentrations; only two samples had residues just above the method detection limit of 25 microg/L. Concentrations of glyphosate in air were predicted to be very small because of negligible volatility. Glyphosate in soils that are directly sprayed will be tightly bound and biologically unavailable and have no residual activity. Concentrations of glyphosate plus Cosmo-Flux will be relatively large in shallow surface waters that are directly oversprayed (maximum instantaneous concentration of 1,229microgAE/L in water 30cm deep); however, no information was available on the number of fields in close proximity to surface waters, and thus it was not possible to estimate the likelihood of such contamination. The formulation used in Colombia, a mixture of glyphosate and Cosmo-Flux, has low toxicity to mammals by all routes of exposure, although some temporary eye irritation may occur. Published epidemiological studies have not suggested a strong or consistent linkage between
Investigating Changes in Serum Biochemical Parameters in Opium Addicts Before and During Addiction Treatment

PubMed Central

Barzehkar, Sedigheh; Gozashti, Mohammad Hossein; Divsalar, Kouros; Mashrouteh, Mahdieh; Darvishi-Lardi, Amir Hossein

2016-01-01

Background Iran is one of the major consumers of opium and opiate substances in the world. Addiction has become a very important issue in the 21st century and an urgent one in Iran. The consumption of this substance leaves a variety of impacts on the human body. The goal of this study is to investigate the changes of the biochemical parameters derived from opiate substances in addicts during their treatment. Methods This is a cross-sectional research that focused on 40 individuals dependent on the consumption of opium. Their blood samples were taken before and during treatment, and their fasting blood sugar (FBS), sodium, calcium, phosphorus, creatinine, urea, uric acid, total protein, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol were measured. Data were analyzed by SPSS using paired t-test. Findings The results showed that serum uric acid, LDL, cholesterol, and the total protein levels significantly decreased during the treatment in comparison with the time before the treatment (P < 0.050). Yet, the serum fasting glucose, urea, creatinine, HDL, triglycerides, calcium, phosphorous, sodium, and potassium showed no significant change the time prior and during the treatment. Conclusion Given the findings of the analysis, opium addiction has a number of destructive impacts on the lipid profile and uric acid. In addition, the level of total protein decreased during the treatment. PMID:28819551
Midazolam Plus Haloperidol as Adjuvant Analgesics to Morphine in Opium Dependent Patients: A Randomized Clinical Trial.

PubMed

Afzalimoghaddam, Mohammad; Edalatifard, Maryam; Nejati, Amir; Momeni, Mehdi; Isavi, Nader; Karimialavijeh, Ehsan

2016-01-01

Tolerance to opioids among opium-dependent patients creates obstacles for proper pain management of these patients in the emergency department (ED). The aim of the present study was to investigate the efficacy of intramuscular (IM) haloperidol plus midazolam on morphine analgesia among opium-dependent patients. Opium-dependent adults who were admitted to the ED for new-onset severe pain in the limbs or abdomen (within 24 hours of admission and a pain score of over six, using a numerical rating scale [NRS]) were recruited. Participants were randomly assigned into two groups. Group A received morphine 0.05 mg/kg intravenously (IV) and a mixture of midazolam 2.5 mg and haloperidol 2.5 mg (diluted in 5 cc of distilled water, IM); group B received morphine 0.05 mg/kg IV and distilled water 5 cc, IM. Measured outcomes were related to: 1) pain intensity; 2) total doses of morphine; 3) changes in hemodynamic status and level of consciousness of patients. NRS scores (zero to 10) before and one, three and six hours following intervention, as well as total doses of morphine, were recorded. We recruited 68 males (78.16%) and 19 females (21.83%). The mean age was 38.28±6.59 years. The pain score in group A declined more rapidly over six hours than that in group B. Moreover, as compared to group B, the amount of morphine use decreased significantly in group A. Based on the present data, adding haloperidol plus midazolam to morphine for pain management improved pain scores and lowered morphine consumption among opium-dependent patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Recent Advances in the Synthesis of Morphine and Related Alkaloids

NASA Astrophysics Data System (ADS)

Chida, Noritaka

Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.
Comparison of Quantitative and Qualitative Dermatoglyphic Characteristics of Opium Addicts with Healthy Individuals

PubMed Central

Mehrpour, Omid; Sheikhazadi, Ardeshir; Barzegar, Afsoon; Husein, Afzal; Malic, Claudia; Sheikhazadi, Elham; Saberi-Anary, Seyed Hossein

2016-01-01

Background Recreational drugs have a significant impact on the lives of drug users, their close families andfriends, as well as their society. Social, psychological, biological, and genetic factors could make a personmore prone to using recreational drugs. Finger and A-B ridges (dermatoglyphics) are formed during the firstand second trimesters of fetal development, under the influence of environmental and genetic factors. Theaim of our study was to investigate and evaluate a possible link between dermatoglyphics and opium usage. Methods The pattern of dermatoglyphics - finger and A-B prints - obtained from a group of opium users(121 patients) was compared to those obtained from a group of opium non-users (121 patients) from Birjand,Iran. The results were analyzed using chi-square, t and Mann–Whitney tests. Findings The results showed that although A-B ridges of palms and fingers in our study group were highercompared to the control group, there was no significant difference between these groups. The only significantdifference was the fingerprint patterns of the left ring finger in the study group, which lacked the arch patternand had less loop patterns. The dominant type of fingerprint in the left ring finger was the whorl. In ouropium user group, the arch and loop fingerprint patterns were heterogeneous and significantly different incomparison with the control group (P < 0.01). Conclusion These findings suggest that a genetic factor may increase the predisposition to recreational drugusage. Further research is required to confirm this possible impact of genetic factors on the addiction process. PMID:27882204
The influence of interplant distance and number of flowers on seed set in dwarf bear-poppy (Arctomecon humilis)

Treesearch

K. T. Harper; Renee Van Buren; Zachary T. Aanderud

2001-01-01

Samples from three isolated populations of the dwarf bear-poppy (Arctomecon humilis Cov.) demonstrate that both flower pollination (fruit set) and seed set per fruit decline as interplant distances increase and the number of flowers per plant declines. Interplant distance and number of flowers per plant tend to interact with reproduction. Seed set per plant is most...
Socio-Cultural Factors Associated with the Initiation of Opium Use in Darab, Iran

ERIC Educational Resources Information Center

Jafari, Siavash; Movaghar, Afarin Rahimi; Craib, Kevin; Baharlou, Souzan; Mathias, Richard

2009-01-01

This study aimed to identify socio-cultural factors facilitating initiation of opium use among drug users in Darab, Iran. A qualitative study using in-depth interviews was conducted. The study began in June 2006 and included 76 drug users, aged 20-43, of whom 95% (72) were male, and 5% (4) were female. The five most common factors facilitating…
Gertrude Stein, opium queen: notes on a mistaken embrace.

PubMed

Solomon, Jeff

2013-01-01

Gertrude Stein was not only a fairly open lesbian but also Jewish, expatriate, and androgynous-all attributes that often retarded mass-market success. Why then was she so popular? The article offers original research highlighting how Stein was constructed as a kind of "opium queen" in the popular American press, and the ways that this decadent, bohemian celebrity persona allowed her to operate as "broadly queer" rather than "specifically gay" in the American cultural imaginary-a negotiation that accounts for the mass-market success rather than censure of The Autobiography of Alice B. Toklas despite the unparalleled visibility of its lesbian erotics.
Unravelling the resistance mechanisms to 2,4-D (2,4-dichlorophenoxyacetic acid) in corn poppy (Papaver rhoeas).

PubMed

Rey-Caballero, Jordi; Menéndez, Julio; Giné-Bordonaba, Jordi; Salas, Marisa; Alcántara, Ricardo; Torra, Joel

2016-10-01

In southern Europe, the intensive use of 2,4-D (2,4-dichlorophenoxyacetic acid) and tribenuron-methyl in cereal crop systems has resulted in the evolution of resistant (R) corn poppy (Papaver rhoeas L.) biotypes. Experiments were conducted to elucidate (1) the resistance response to these two herbicides, (2) the cross-resistant pattern to other synthetic auxins and (3) the physiological basis of the auxin resistance in two R (F-R213 and D-R703) populations. R plants were resistant to both 2,4-D and tribenuron-methyl (F-R213) or just to 2,4-D (D-R703) and both R populations were also resistant to dicamba and aminopyralid. Results from absorption and translocation experiment revealed that R plants translocated less [14C]-2,4-D than S plants at all evaluation times. There was between four and eight-fold greater ethylene production in S plants treated with 2,4-D, than in R plants. Overall, these results suggest that reduced 2,4-D translocation is the resistance mechanism in synthetic auxins R corn poppy populations and this likely leads to less ethylene production and greater survival in R plants. Copyright © 2016 Elsevier B.V. All rights reserved.
Effect of unconventional oilseeds (safflower, poppy, hemp, camelina) on in vitro ruminal methane production and fermentation.

PubMed

Wang, Shaopu; Kreuzer, Michael; Braun, Ueli; Schwarm, Angela

2017-08-01

Dietary supplementation with oilseeds can reduce methane emission in ruminants, but only a few common seeds have been tested so far. This study tested safflower (Carthamus tinctorius), poppy (Papaver somniferum), hemp (Cannabis sativa), and camelina (Camelina sativa) seeds in vitro using coconut (Cocos nucifera) oil and linseed (Linum usitatissimum) as positive controls. All the tested oilseeds suppressed methane yield (mL g -1 dry matter, up to 21%) compared to the non-supplemented control when provided at 70 g oil kg -1 dry matter, and they were as effective as coconut oil. Safflower and hemp were more effective than linseed (21% and 18% vs. 10%), whereas the effects of poppy and camelina were similar to linseed. When methane was related to digestible organic matter, only hemp and safflower seeds and coconut oil were effective compared to the non-supplemented control (up to 11%). The level of methanogenesis and the ratios of either the n-6:n-3 fatty acids or C 18 :2 :C 18 :3 in the seed lipids were not related. Unconventional oilseeds widen the spectrum of oilseeds that can be used in dietary methane mitigation. In vivo confirmation of their methane mitigating effect is still needed, and their effects on animal performance still must be determined. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.
Relationships of dissociative disorders and personality traits in opium addicts on methadone treatment.

PubMed

Ghafarinezhad, Alireza; Rajabizadeh, Ghodratollah; Shahriari, Vahid

2013-01-01

Drug abuse is a major public health problem. Some believe that when dissociation fails to defend against emotional, physical, or sexual trauma, the person will find relief from unpleasant thoughts and emotions in opium use. On the other hand, personality disorders are considered as important predictors of treatment outcomes in drug abusers. Due to lack of adequate research in this regard, we evaluated dissociative disorders and personality traits of opium addicts on methadone treatment. This cross-sectional analytic study included 111 non-psychotic subjects on methadone treatment (case group) and 69 non-addicts (control group). After recording demographic characteristics, Dissociative Experiences Scale (DES) and Millon Multiaxial Inventory III were applied to assess dissociative symptoms and clinical personality patterns of all participants. Dissociative symptoms were significantly more common in the case group than in the control group (P = 0.044). While hysterionic personality disorder was more frequent in the control group (P = 0.008), sadistic, antisocial, and schizotypal personality disorders were significantly more common in the case group (P = 0.008, 0.002, and 0.023, respectively). We found relations between history of drug dependence, dissociative symptoms, and personality disorders. Therefore, the mentioned disorders need to be kept in mind while planning addiction treatment modalities and identifying high risk groups.
Common Bile Duct (CBD) diameter in opium-addicted men: Comparison with non-addict controls.

PubMed

Zahedi-Nejad, Nina; Narouei, Shahin; Fahimy, Farnaz

2010-07-01

Opium and its derivatives are widely abused throughout the world. Recent case reports and a few limited studies have suggested that opiates cause dilation of the common bile duct of the abusers. Our case-control study, lasting 7.5 months, investigated 121 male adult addicts and 142 non-addicted controls for biliary tract diameters, using ultrasonography. The study was conducted in Bahonar Hospital in Kerman. Neither the addiction cases nor the non-addict controls revealed any hepatobiliary tract symptoms. The subjects were asked to fill in a questionnaire. After the exclusion of the symptomatic cases, ultrasound examinations were carried out and the findings from questionnaires and US examinations were recorded. The mean ±SD diameter of the common bile duct was 4.78±2.58 for addicts and 3.37±2.25 for non-addicts. CBD wall thickness was 1.969±0.61 mm in addicts versus 1.73±0.631 in non-addicts. The differences were statistically significant. According to the multivariate analysis, the duration of opium abuse was a significant factor. We concluded that CBD dilation and increased CBD wall thickness can be expected in people with a prolonged history of opiate addiction.
Cannabis and Opium Abuse Patterns and Their Associated Complications in a Sample of Young Iranians

ERIC Educational Resources Information Center

Attari, Mohammad Ali; Asgary, Sedigheh; Shahrokhi, Shahnaz; Naderi, Gholam Ali; Shariatirad, Schwann

2012-01-01

The prevalence of drug abuse has been reported to be up to 17.0% in Iran. The aim of this study was to investigate the prevalence of two frequently abused substances--cannabis and opium--in samples of the young population in Isfahan, Iran. In a survey done from January 2005 to December 2006, 537 individuals aged 13-20 years were recruited using a…
Dispersive liquid-liquid microextraction followed by high-performance liquid chromatography-ultraviolet detection to determination of opium alkaloids in human plasma.

PubMed

Ahmadi-Jouibari, Toraj; Fattahi, Nazir; Shamsipur, Mojtaba; Pirsaheb, Meghdad

2013-11-01

A novel, simple, rapid and sensitive dispersive liquid-liquid microextraction method based on the solidification of floating organic drop (DLLME-SFO) combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was used to determine opium alkaloids in human plasma. During the extraction procedure, plasma protein was precipitated by using a mixture of zinc sulfate solution and acetonitrile. Some effective parameters on extraction were studied and optimized. Under the optimum conditions (extraction solvent: 30.0 μl 1-undecanol; disperser solvent: 470 μl acetone; pH: 9; salt addition: 1%(w/v) NaCl and extraction time: 0.5 min), calibration curves are linear in the range of 1.5-1000 μgl(-1) and limit of detections (LODs) are in the range of 0.5-5 μgl(-1). The relative standard deviations (RSDs) for 100 μgl(-1) of morphine and codeine, 10.0 μgl(-1) of papaverine and 20.0 μgl(-1) of noscapine in diluted human plasma are in the range of 4.3-7.4% (n=5). Finally, the method was successfully applied in the determination of opium alkaloids in the actual human plasma samples. The relative recoveries of plasma samples spiked with alkaloids are 88-110.5%. The obtained results show that DLLME-SFO combined with HPLC-UV is a fast and simple method for the determination of opium alkaloids in human plasma. Copyright © 2013 Elsevier B.V. All rights reserved.
Experiences of Opium Dependents from Performance of Methadone Centers of Kerman, Iran

PubMed Central

Banazadeh Mahani, Nabi; Kheradmand, Ali; Abedi, Heidarali

2009-01-01

Background: To assess patients' satisfaction and to evaluate methadone therapy program, it is important to understand the experiences of opium dependents during the treatment period in methadone centers and determine the quality of this program and revise standards based on that. This study aimed to describe the nature and structure of patients' experiences during treatment in methadone centers. Methods: This was a qualitative method using phenomenology. Sampling was purposive and the participants were selected from opium dependents referred to Kerman methadone centers during 2007. Sampling continued until data saturation and the sample size was 32. Colaizzi's method was applied for data analysis. Findings: The findings of this study included 27 codes categorized in four main groups: experiences of structure, personnel, patients, and regulations. These four categories showed the main structure of experiences in methadone centers. Conclusion: Lack of treatment centers in near-by cities or the problems of those centers suggest that it is necessary to establish new centers or solve the problems of centers in near-by cities. The type of patients referring to the centers plays a role in treatment process. The regular presence of physicians and other personnel and their concerns and care for patients as well as longer working hours of the centers have roles in patients' satisfaction and increase of consistency with treatment. Discussing the rules and regulations of the center with patients including the obligatory of daily reference to the center to obtain medicine and injections sound necessary. Also, it is necessary to find ways for solving problems of urine tests. PMID:24494087
Determinants of Gastroesophageal Reflux Disease, Including Hookah Smoking and Opium Use– A Cross-Sectional Analysis of 50,000 Individuals

PubMed Central

Islami, Farhad; Nasseri-Moghaddam, Siavosh; Pourshams, Akram; Poustchi, Hossein; Semnani, Shahryar; Kamangar, Farin; Etemadi, Arash; Merat, Shahin; Khoshnia, Masoud; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Abnet, Christian C.; Boffetta, Paolo; Malekzadeh, Reza

2014-01-01

Background Gastroesophageal reflux disease (GERD) is a common cause of discomfort and morbidity worldwide. However, information on determinants of GERD from large-scale studies in low- to medium-income countries is limited. We investigated the factors associated with different measures of GERD symptoms, including frequency, patient-perceived severity, and onset time. Methods We performed a cross-sectional analysis of the baseline data from a population-based cohort study of ∼50,000 individuals in in Golestan Province, Iran. GERD symptoms in this study included regurgitation and/or heartburn. Results Approximately 20% of participants reported at least weekly symptoms. Daily symptoms were less commonly reported by men, those of Turkmen ethnicity, and nass chewers. On the other hand, age, body mass index, alcohol drinking, cigarette smoking, opium use, lower socioeconomic status, and lower physical activity were associated with daily symptoms. Most of these factors showed similar associations with severe symptoms. Women with higher BMI and waist to hip ratio were more likely to report frequent and severe GERD symptoms. Hookah smoking (OR 1.34, 95% CI 1.02–1.75) and opium use (OR 1.70, 95% CI 1.55–1.87) were associated with severe symptoms, whereas nass chewing had an inverse association (OR 0.87, 95% CI 0.76–0.99). After exclusion of cigarette smokers, hookah smoking was still positively associated and nass chewing was inversely associated with GERD symptoms (all frequencies combined). Conclusion GERD is common in this population. The associations of hookah and opium use and inverse association of nass use with GERD symptoms are reported for the first time. Further studies are required to investigate the nature of these associations. Other determinants of GERD were mostly comparable to those reported elsewhere. PMID:24586635

Narcosis and nightshade.

PubMed Central

Carter, A. J.

1996-01-01

Although this year marks the 150th anniversary of the discovery of modern surgical anaesthesia, surgery itself has a much longer history. It is well known that extracts from the opium poppy, Papaver somniferum, were used to dull the pain of surgery during ancient times but less well known that extracts from plants with sedative powers often accompanied them, producing primitive anaesthesia. Most of these sedative plants were members of a large botanical family, the Solanaceae. This paper describes some of them and discusses the ways in which they were administered. It also explains why, during the middle ages, these primitive techniques went out of use but how none the less they provided Shakespeare with the inspiration for some of his greatest plays. When the active principal of the Solanaceae was identified as scopolamine, it came to play a part in 20th century anaesthesia. The combination of omnopon and scopolamine lives on as a premedication, and the presence of poppy heads and mandrake roots on the arms of today's Association of Anaesthetists serves to remind us of the speciality's links with its past. Images p1630-a p1631-a p1631-b p1631-c p1632-a p1632-b PMID:8991015
Noscapine protects OLN-93 oligodendrocytes from ischemia-reperfusion damage: Calcium and nitric oxide involvement.

PubMed

Nadjafi, S; Ebrahimi, S-A; Rahbar-Roshandel, N

2015-12-01

This study was carried out to evaluate the effects of noscapine, a benzylisoquinoline alkaloid from opium poppy, on oligodendrocyte during ischemia/reperfusion-induced excitotoxic injury. Changes in intracellular calcium levels due to chemical ischemia and nitric oxide (NO) production during ischemia/reperfusion were evaluated as the hallmarks of ischemia-derived excitotoxic event. OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. 30- or 60-minute-oxygen-glucose deprivation/24 hours reperfusion were used to induce excitotoxicity. MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used to evaluate cell viability. Ratiometric fluorescence microscopy using Ca(2+)-sensitive indicator Fura-2/AM was utilized to assess intracellular calcium levels. NO production was evaluated by Griess method. Noscapine (4 μM) significantly attenuated intracellular Ca(2+) elevation (P < 0.001). Also, noscapine significantly decreased NO production during a 30-minute oxygen-glucose deprivation/reperfusion (P < 0.01). The inhibitory effect of noscapine (4 μM) on intracellular Ca(2+) was greater than ionotropic glutamate receptors antagonists. Noscapine is protective against ischemia/reperfusion-induced excitotoxic injury in OLN-93 oligodendrocyte. This protective effect seems to be related to attenuation of intracellular Ca(2+) overload and NO production.
Molecular cloning and characterization of a novel freezing-inducible DREB1/CBF transcription factor gene in boreal plant Iceland poppy (Papaver nudicaule).

PubMed

Huang, Zhuo; He, Jiao; Zhong, Xiao-Juan; Guo, Han-Du; Jin, Si-Han; Li, Xi; Sun, Ling-Xia

2016-01-01

DREB1 of the AP2/ERF superfamily plays a key role in the regulation of plant response to low temperatures. In this study, a novel DREB1/CBF transcription factor, PnDREB1, was isolated from Iceland poppy (Papaver nudicaule), a plant adaptive to low temperature environments. It is homologous to the known DREB1s of Arabidopsis and other plant species. It also shares similar 3D structure, and conserved and functionally important motifs with DREB1s of Arabidopsis. The phylogenetic analysis indicated that the AP2 domain of PnDREB1 is similar to those of Glycine max, Medicago truncatula, and M. sativa. PnDREB1 is constitutively expressed in diverse tissues and is increased in roots. qPCR analyses indicated that PnDREB1 is significantly induced by freezing treatment as well as by abscissic acid. The expression levels induced by freezing treatment were higher in the variety with higher degree of freezing tolerance. These results suggested that PnDREB1 is a novel and functional DREB1 transcription factor involved in freezing response and possibly in other abiotic stresses. Furthermore, the freezing-induction could be suppressed by exogenous gibberellins acid, indicating that PnDREB1 might play some role in the GA signaling transduction pathway. This study provides a basis for better understanding the roles of DREB1 in adaption of Iceland poppy to low temperatures.
A history of intraspinal analgesia, a small and personal journey.

PubMed

Krames, Elliot S

2012-01-01

There is a large and robust literature on the spinal use of opioids and non-opioids alike, but unless one is my age and older, very few persons know how we got here. This small history offering tells us how we got to where we are today regarding the science, clinical uses, and management of intraspinal analgesia. I have reviewed the literature bases of Google Scholar and the National Library of Medicine using the key words: history, opium, spinal analgesia, spinal morphine, intrathecal (IT), opioid receptors, endogenous opioids, IT delivery of opioids, and IT side-effects/complications. In this personal review of the history of intraspinal analgesia, I relate my own early and later experiences of the science and clinical uses of intraspinal morphine, other opioids, and non-opioids alike to a historical context. This review outlines a rather small history of opium, the historical use of opium and its various compounds, and the search for and answer to the question, "why was the poppy created for wondrous medicinal uses for mankind?" This search led to the discovery of endogenous opioid like chemicals, the discovery of opiate receptors for these endogenous opioids, the first uses of intraspinal opioids in animal models and man, and, finally, our understanding of the appropriate and inappropriate clinical uses of intraspinal analgesia. Within this paper, I acknowledge the works of my colleagues and the "heroes" who have laid the foundation for our understanding of intraspinal analgesia. The history of the use of intraspinal analgesia is rich and guides us to advance the science and clinical use of intraspinal analgesia without reinventing the wheel. © 2012 International Neuromodulation Society.
The opium wars revisited as US forces tobacco exports in Asia.

PubMed Central

Chen, T T; Winder, A E

1990-01-01

The tobacco industry has lobbied successfully to obtain the support of the United States government for opening Asian Markets to American tobacco products. This paper comments on two issues arising from these efforts: the development of an atmosphere of invasion and resistance to invasion in Asia; and the change in the image of the United States in Asian nations from that of a leader in health to that of an exporter of death. The threat of sanctions and the effects of the open market and United States tobacco company advertising in Japan, Taiwan, and South Korea are noted. Parallels are drawn between the opium wars a century and a half ago in China and the current threat of trade sanctions. Reacting to American policy, an Asia-Pacific Association for Control of Tobacco has been formed and linked with the US Coalition Against Smoking. PMID:2343946
Drug Policy and Indigenous Peoples.

PubMed

Burger, Julian; Kapron, Mary

2017-06-01

This paper identifies the principal concerns of indigenous peoples with regard to current international treaties on certain psychoactive substances and policies to control and eradicate their production, trafficking, and sale. Indigenous peoples have a specific interest in the issue since their traditional lands have become integrated over time into the large-scale production of coca, opium poppy, and cannabis crops, in response to high demand from the American and European markets, among others. As a consequence, indigenous peoples are persecuted because of their traditional use of these and other plant-based narcotics and hallucinogens. They are also victims of the drug producers who remove them from their lands or forcibly recruit them into the production process. As indigenous peoples are caught in the violent world of illicit drug production, law enforcement often targets them first, resulting in disproportionate rates of criminalization and incarceration.
Drug Policy and Indigenous Peoples

PubMed Central

Kapron, Mary

2017-01-01

Abstract This paper identifies the principal concerns of indigenous peoples with regard to current international treaties on certain psychoactive substances and policies to control and eradicate their production, trafficking, and sale. Indigenous peoples have a specific interest in the issue since their traditional lands have become integrated over time into the large-scale production of coca, opium poppy, and cannabis crops, in response to high demand from the American and European markets, among others. As a consequence, indigenous peoples are persecuted because of their traditional use of these and other plant-based narcotics and hallucinogens. They are also victims of the drug producers who remove them from their lands or forcibly recruit them into the production process. As indigenous peoples are caught in the violent world of illicit drug production, law enforcement often targets them first, resulting in disproportionate rates of criminalization and incarceration. PMID:28630559
Comparison of oilseed yields: a preliminary review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duke, J.A.; Bagby, M.O.

It was assumed that for most oilseed crops, 90% of the oil yield might be considered as profit. To compare oil seeds, pertinent portions of the yield and energy paragraphs from a summary published by Dr. Duke for DOE Grant No. 59-2246-1-6-054-0 with Dr. Bagby as ADODR were reproduced. The seed yields ranged from 200 to 14,000 kg/ha, the low one too low to consider and the high one suspiciously high. The yield of 14,000 kg oil per hectare is equivalent to more than 30 barrels of oil per hectare. The energy species included ambrette, tung-oil tree, cashew, wood-oil tree,more » mu-oil tree, peanut, mustard greens; rape, colza; black mustard, turnip, safflower, colocynth, coconut, crambe, African oil palm, soybean, cotton, sunflower, Eastern black walnut, Engligh walnut, meadow foam, flax, macadamia nuts, opium poppy, perilla, almond, castorbean, Chinese tallow tree, sesame, jojoba, yellow mustard, stokes' aster, and Zanzibar oilvine. 1 table. (DP)« less
Natural products for chronic cough: Text mining the East Asian historical literature for future therapeutics.

PubMed

Shergis, Johannah Linda; Wu, Lei; May, Brian H; Zhang, Anthony Lin; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie Changli

2015-08-01

Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough. © The Author(s) 2015.
Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients (POPPI): protocol for a cluster-randomised clinical trial of a complex intervention

PubMed Central

Richards-Belle, Alvin; Mouncey, Paul R; Wade, Dorothy; Brewin, Chris R; Emerson, Lydia M; Grieve, Richard; Harrison, David A; Harvey, Sheila; Howell, David; Mythen, Monty; Sadique, Zia; Smyth, Deborah; Weinman, John; Welch, John; Rowan, Kathryn M

2018-01-01

Introduction Acute psychological stress, as well as unusual experiences including hallucinations and delusions, are common in critical care unit patients and have been linked to post-critical care psychological morbidity such as post-traumatic stress disorder (PTSD), depression and anxiety. Little high-quality research has been conducted to evaluate psychological interventions that could alleviate longer-term psychological morbidity in the critical care unit setting. Our research team developed and piloted a nurse-led psychological intervention, aimed at reducing patient-reported PTSD symptom severity and other adverse psychological outcomes at 6 months, for evaluation in the POPPI trial. Methods and analysis This is a multicentre, parallel group, cluster-randomised clinical trial with a staggered roll-out of the intervention. The trial is being carried out at 24 (12 intervention, 12 control) NHS adult, general, critical care units in the UK and is evaluating the clinical effectiveness and cost-effectiveness of a nurse-led preventative psychological intervention in reducing patient-reported PTSD symptom severity and other psychological morbidity at 6 months. All sites deliver usual care for 5 months (baseline period). Intervention group sites are then trained to carry out the POPPI intervention, and transition to delivering the intervention for the rest of the recruitment period. Control group sites deliver usual care for the duration of the recruitment period. The trial also includes a process evaluation conducted independently of the trial team. Ethics and dissemination This protocol was reviewed and approved by the National Research Ethics Service South Central - Oxford B Research Ethics Committee (reference: 15/SC/0287). The first patient was recruited in September 2015 and results will be disseminated in 2018. The results will be presented at national and international conferences and published in peer reviewed medical journals. Trial registration number
Neuroprotective effect of noscapine on cerebral oxygen-glucose deprivation injury.

PubMed

Vahabzadeh, Gelareh; Rahbar-Roshandel, Nahid; Ebrahimi, Soltan-Ahmad; Mahmoudian, Massoud

2015-04-01

The present study aims to investigate the effect of noscapine (0.5-2.5 μM), an alkaloid from the opium poppy, on primary murine fetal cortical neurons exposed to oxygen-glucose deprivation (OGD), an in vitro model of ischemia. Cells were transferred to glucose-free DMEM and were exposed to hypoxia in a small anaerobic chamber. Cell viability and nitric oxide production were evaluated by MTT assay and the Griess method, respectively. The neurotoxicities produced by all three hypoxia durations tested were significantly inhibited by 0.5 μM noscapine. Increasing noscapine concentration up to 2.5 μM produced a concentration-dependent inhibition of neurotoxicity. Pretreatment of cells with MK-801 (10 μM), a non-competitive NMDA antagonist, and nimodipine (10nM), an L-type Ca(2+) channel blockers, increased cell viability after 30 min OGD, while the application of NBQX (30 μM), a selective AMPA-kainate receptor antagonist partially attenuated cell injury. Subsequently, cells treated with noscapine in the presence of thapsigargin (1 μM), an inhibitor of endoplasmic reticulum Ca(2+) ATPases. After 60 min OGD, noscapine could inhibit the cell damage induced by thapsigargin. However, noscapine could not reduce cell damage induced by 240 min OGD in the presence of thapsigargin. Noscapine attenuated nitric oxide (NO) production in cortical neurons after 30 min OGD. We concluded that noscapine had a neuroprotective effect, which could be due to its interference with multiple targets in the excitotoxicity process. These effects could be mediated partially by a decrease in NO production and the modulation of intracellular calcium levels. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
[Rapid screening the alkaloids of poppy shell in hot pot condiment, beef noodle soup and seasoning by direct analysis in real time-tandem mass spectrometry].

PubMed

Zhang, Baile; Gao, Lihong; Xie, Yingshuang; Zhou, Wei; Chen, Xiaofeng; Lei, Chunni; Zhang, Huan

2017-07-08

A direct analysis in real time tandem mass spectrometry (DART-MS/MS) method was established for quickly screening five illegally added alkaloids of poppy shell from the hot pot condiment, beef noodle soup and seasoning. The samples were extracted and purified by acetonitrile, and then injected under the conditions of ionization temperature of 300℃, grid electrode voltage of 150 V and sampling rate of 0.8 mm/s using DART in the positive ion mode. The determination was conducted by tandem mass spectrometry in positive ESI mode under multiple reaction monitoring (MRM) mode. The method is simple and rapid, and can meet the requirement of rapid screening and analysis of large quantities of samples.
Modulation of benzylisoquinoline alkaloid biosynthesis by heterologous expression of CjWRKY1 in Eschscholzia californica cells

PubMed Central

Shimada, Tomoe; Motomura, Yukiya; Sato, Fumihiko

2017-01-01

Transcription factors control many processes in plants and have high potentials to manipulate specialized metabolic pathways. Transcriptional regulation of the biosynthesis of monoterpenoid indole alkaloids (MIAs), nicotine alkaloids, and benzylisoquinoline alkaloids (BIAs) has been characterized using Catharanthus roseus, Nicotiana and Coptis plants. However, metabolic engineering in which specific transcription factors are used in alkaloid biosynthesis is limited. In this study, we characterized the effects of ectopic expression of CjWRKY1, which is a transcriptional activator with many targets in BIA biosynthesis in Coptis japonica (Ranunculaceae) and Eschscholzia californica (California poppy, Papaveraceae). Heterologous expression of CjWRKY1 in cultured California poppy cells induced increases in transcripts of several genes encoding BIA biosynthetic enzymes. Metabolite analyses indicated that the overexpression of the CjWRKY1 gene also induced increases in the accumulation of BIAs such as sanguinarine, chelerythrine, chelirubine, protopine, allocryptopine, and 10-hydroxychelerythrine in the culture medium. Previous characterization of EcbHLH1 and current results indicated that both transcription factors, WRKY1 and bHLH1, are substantially involved in the regulation of BIA biosynthesis. We discuss the function of CjWRKY1 in E. californica cells and its potential for metabolic engineering in BIA biosynthesis. PMID:29077729
How to find non-dependent opiate users: a comparison of sampling methods in a field study of opium and heroin users.

PubMed

Korf, Dirk J; van Ginkel, Patrick; Benschop, Annemieke

2010-05-01

The first aim is to better understand the potentials and limitations of different sampling methods for reaching a specific, rarely studied population of drug users and for persuading them to take part in a multidisciplinary study. The second is to determine the extent to which these different methods reach similar or dissimilar segments of the non-dependent opiate-using population. Using ethnographic fieldwork (EFW) and targeted canvassing (TARC; small newspaper advertisements and website announcements), supplemented by snowball referrals, we recruited and interviewed 127 non-dependent opiate users (lifetime prevalence of use 5-100 times; 86.6% had used heroin and 56.7% opium). Average age was 39.0; 66.1% were male and 33.9% female. In addition to opiates, many respondents had wide experience with other illicit drugs. The majority had non-conventional lifestyles. Both EFW and TARC yielded only limited numbers of snowball referrals. EFW requires specific skills, is labour-intensive, thus expensive, but allows unsuitable candidates to be excluded faster. Respondents recruited through EFW were significantly more likely to have experience with opium and various drugs other than opiates. TARC resulted in larger percentages of women and respondents with conventional lifestyles. TARC is less labour-intensive but requires more time for screening candidates; its cost-effectiveness depends on the price of advertising for the recruitment. Different methods reach different segments of the population of non-dependent opiate users. It is useful to employ a multi-method approach to reduce selectivity. Copyright 2009 Elsevier B.V. All rights reserved.
Mining of the Uncharacterized Cytochrome P450 Genes Involved in Alkaloid Biosynthesis in California Poppy Using a Draft Genome Sequence

PubMed Central

Hori, Kentaro; Yamada, Yasuyuki; Purwanto, Ratmoyo; Minakuchi, Yohei; Toyoda, Atsushi; Hirakawa, Hideki

2018-01-01

Abstract Land plants produce specialized low molecular weight metabolites to adapt to various environmental stressors, such as UV radiation, pathogen infection, wounding and animal feeding damage. Due to the large variety of stresses, plants produce various chemicals, particularly plant species-specific alkaloids, through specialized biosynthetic pathways. In this study, using a draft genome sequence and querying known biosynthetic cytochrome P450 (P450) enzyme-encoding genes, we characterized the P450 genes involved in benzylisoquinoline alkaloid (BIA) biosynthesis in California poppy (Eschscholzia californica), as P450s are key enzymes involved in the diversification of specialized metabolism. Our in silico studies showed that all identified enzyme-encoding genes involved in BIA biosynthesis were found in the draft genome sequence of approximately 489 Mb, which covered approximately 97% of the whole genome (502 Mb). Further analyses showed that some P450 families involved in BIA biosynthesis, i.e. the CYP80, CYP82 and CYP719 families, were more enriched in the genome of E. californica than in the genome of Arabidopsis thaliana, a plant that does not produce BIAs. CYP82 family genes were highly abundant, so we measured the expression of CYP82 genes with respect to alkaloid accumulation in different plant tissues and two cell lines whose BIA production differs to estimate the functions of the genes. Further characterization revealed two highly homologous P450s (CYP82P2 and CYP82P3) that exhibited 10-hydroxylase activities with different substrate specificities. Here, we discuss the evolution of the P450 genes and the potential for further genome mining of the genes encoding the enzymes involved in BIA biosynthesis. PMID:29301019
Structure-based discovery of opioid analgesics with reduced side effects.

PubMed

Manglik, Aashish; Lin, Henry; Aryal, Dipendra K; McCorvy, John D; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F; Giguère, Patrick M; Löber, Stefan; Da Duan; Scherrer, Grégory; Kobilka, Brian K; Gmeiner, Peter; Roth, Bryan L; Shoichet, Brian K

2016-09-08

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent G i activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids.
Structure–based discovery of opioid analgesics with reduced side effects

PubMed Central

Manglik, Aashish; Lin, Henry; Aryal, Dipendra K.; McCorvy, John D.; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C.; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F.; Giguère, Patrick M.; Löber, Stefan; Duan, Da; Scherrer, Grégory; Kobilka, Brian K.; Gmeiner, Peter; Roth, Bryan L.; Shoichet, Brian K.

2016-01-01

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids—which include fatal respiratory depression—are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21—a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids. PMID:27533032
Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics.

PubMed

Trang, Tuan; Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W; Gutstein, Howard; Cahill, Catherine M

2015-10-14

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. Copyright © 2015 the authors 0270-6474/15/3513879-10$15.00/0.
Pain and Poppies: The Good, the Bad, and the Ugly of Opioid Analgesics

PubMed Central

Al-Hasani, Ream; Salvemini, Daniela; Salter, Michael W.; Gutstein, Howard

2015-01-01

Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward. SIGNIFICANCE STATEMENT Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids. PMID:26468188
The monitoring of trade in and control of psychotropic substances to guard against their diversion.

PubMed

Bayer, I

1983-01-01

The establishment of international control of opiates has been an important achievement of the international community; this is substantiated by the fact that, at the beginning of this century, legally manufactured morphine and heroin were the principal sources of illicit supply, whereas at present the illicit traffic in these drugs is supplied from illicit sources. The poppy straw process has helped to promote measures to control opium poppy cultivation in a number of European countries; Turkey has been a successful example of such control. The present large-scale illicit traffic in cannabis resin and cocaine is the consequence of the lack of the implementation of provisions of the Single Convention on Narcotic Drugs, 1961, to control the cannabis plant and the coca bush at the national level. The provisions of the 1971 Convention on Psychotropic Substances, being largely a result of international compromise, are not designed in the best possible way to prevent the diversion of psychotropic substances from legal sources to illicit channels. There are no appropriate provisions for the control and monitoring of international transactions. There is a discrepancy between the rather limited scope of international control of substances listed in schedules III and IV of the 1971 Convention and the much larger scope of control of hypnotics, sedatives and tranquillizers at national levels. The provisions of the 1971 Convention, however, constitute a legal basis for bilateral and multilateral actions for the detection of suspected diversion cases, and offer possibilities of promoting the prevention of diversion of psychotropic substances. At present, the relationship between the control of psychotropic drugs, including the prevention of diversion and the organization of the national drug supply system, as well as the efficacy of national control over pharmaceutical products, has not been fully recognized by the international community.

Opium addiction as an independent risk factor for coronary microvascular dysfunction: A case-control study of 250 consecutive patients with slow-flow angina.

PubMed

Esmaeili Nadimi, Ali; Pour Amiri, Farah; Sheikh Fathollahi, Mahmood; Hassanshahi, Gholamhossien; Ahmadi, Zahra; Sayadi, Ahmad Reza

2016-09-15

Approximately 20% to 30% of patients who undergo coronary angiography for assessment of typical cardiac chest pain display microvascular coronary dysfunction (MCD). This study aimed to determine potential relationships between baseline clinical characteristics and likelihood of MCD diagnosis in a large group of patients with stable angina symptoms, positive exercise test and angiographic ally normal epicardial coronary arteries. This cross-sectional study included 250 Iranian with documented evidence of cardiac ischemia on exercise testing, class I or II indication for coronary angiography, and either: (1) angiographically normal coronary arteries and diagnosis of MCD with slow-flow phenomenon, or (2) normal angiogram and no evidence of MCD. All patients completed a questionnaire designed to capture key data including clinical demographics, past medical history, and social factors. Data was evaluated using single and multivariable logistic regression models to identify potential individual patient factors that might help to predict a diagnosis of MCD. 125 (11.2% of total) patients were subsequently diagnosed with MCD. 125 consecutive control subjects were selected for comparison. The mean age was similar among the two groups (52.38 vs. 53.26%, p=ns), but there was a higher proportion of men in the study group compared to control (42.4 vs. 27.2%, p=0.012). No significant relationships were observed between traditional cardiovascular risk factors (diabetes, hypertension, and dyslipidemia) or body mass index (BMI), and likelihood of MCD diagnosis. However, opium addiction was found to be an independent predictor of MCD on single and multivariable logistic regression model (OR=3.575, 95%CI: 1.418-9.016; p=0.0069). We observed a significant relationship between opium addiction and microvascular angina. This novel finding provides a potential mechanistic insight into the pathogenesis of MCD with slow-flow phenomenon. Copyright © 2016 Elsevier Ireland Ltd. All rights
Biotransformation and tissue distribution of protopine and allocryptopine and effects of Plume Poppy Total Alkaloid on liver drug-metabolizing enzymes.

PubMed

Huang, Ya-Jun; Cheng, Pi; Zhang, Zhuo-Yi; Tian, Shi-Jie; Sun, Zhi-Liang; Zeng, Jian-Guo; Liu, Zhao-Ying

2018-01-11

In this study, the biotransformation in the plasma, urine and feces of rats following oral administration of protopine (PRO) and allocryptopine (ALL)were explored using HPLC-QqTOF MS. An HPLC-MS/MS method for the determination of tissues was developed and applied to the tissue distribution study in rats following intragastric administration of Plume Poppy Total Alkaloid for 3 weeks. A total of ten PRO metabolites and ten ALL metabolites were characterized in rats in vivo. Among these metabolites, six PRO metabolites and five ALL metabolites were reported for the first time. The predicated metabolic pathways including ring cleavage, demethylation following ring cleavage, and glucuronidation were proposed. The low-concentration residue of PRO and ALL in various tissues was detected at 24 h and 48 h after dosing, which indicated that both compounds could be widely distributed in tissues and exist as low levels of residue. The activities of erythromycin N-demethylase, aminopyrine N-demethylase and NAD (P)H quinone oxidoreductase in female rats can be induced post-dose, but these activities were inhibited in male rats. The proposed biotransformation and residues of PRO and ALL and their effects on enzymes may provide a basis for clarifying the metabolism and interpreting pharmacokinetics.
Characterization and origin of the 'B' and 'C' compounds in the acid/neutral forensic signatures of heroin - products from the acylation of porphyroxine and subsequent hydrolysis.

PubMed

Casale, John F; Casale, Ellen S; Toske, Steven G; Hays, Patrick A; Panicker, Sini

2017-03-01

Two significant compounds often found in the gas chromatographic analysis of the acid/neutral extracts from illicit heroin have remained uncharacterized for 30 years. The unknown compounds are referred to as the 'B' and 'C' compounds. It has been postulated that these compounds arise from acetylation of porphyroxine, a rhoeadine alkaloid found at trace levels in the opium poppy, Papaver somniferum. Porphyroxine was isolated from opium and acetylated to produce N,O 8 -diacetylporphyroxine. Mild hydrolysis produced N,O 8 -diacetyl-O 14 -desmethyl-epi-porphyroxine (the C compound) and N-acetyl-O 14 -desmethyl-epi-porphyroxine (the B compound). Both N,O 8 -diacetyl-O 14 -desmethyl-epi-porphyroxine and N-acetyl-O 14 -desmethyl-epi-porphyroxine were determined to be C-14 epimers of porphyroxine and N,O 8 -diacetylporphyroxine. The non-epimerized isomers of the B and C compounds were also detected in illicit heroin, but at much lower levels. Chromatographic and spectroscopic data are presented for the aforementioned compounds. The presence/absence and relative concentrations of these compounds is presented for the four types of heroin (Southwest Asian, South American, Southeast Asian, and Mexican). The prevalence of detection for the B and C compounds are Southwest Asian = 92-93%, South American = 64-72%, Southeast Asian = 45-49%, and Mexican ≤ 3%. When detected, the overall trend of relative concentrations of dicaetylporhyroxine, the B-compound, and C-compound is Southwest Asian > South American > Southeast Asian, each by an order of magnitude. These compounds were rarely detected in Mexican heroin. The presence/absence and relative concentrations of these compounds provide pertinent forensic signature characteristics that significantly enhance the final regional classifications. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
Blind column selection protocol for two-dimensional high performance liquid chromatography.

PubMed

Burns, Niki K; Andrighetto, Luke M; Conlan, Xavier A; Purcell, Stuart D; Barnett, Neil W; Denning, Jacquie; Francis, Paul S; Stevenson, Paul G

2016-07-01

The selection of two orthogonal columns for two-dimensional high performance liquid chromatography (LC×LC) separation of natural product extracts can be a labour intensive and time consuming process and in many cases is an entirely trial-and-error approach. This paper introduces a blind optimisation method for column selection of a black box of constituent components. A data processing pipeline, created in the open source application OpenMS®, was developed to map the components within the mixture of equal mass across a library of HPLC columns; LC×LC separation space utilisation was compared by measuring the fractional surface coverage, fcoverage. It was found that for a test mixture from an opium poppy (Papaver somniferum) extract, the combination of diphenyl and C18 stationary phases provided a predicted fcoverage of 0.48 and was matched with an actual usage of 0.43. OpenMS®, in conjunction with algorithms designed in house, have allowed for a significantly quicker selection of two orthogonal columns, which have been optimised for a LC×LC separation of crude extractions of plant material. Copyright © 2016 Elsevier B.V. All rights reserved.
The pattern of intravenous drug use and associated criminal activity in patients on a methadone treatment waiting list.

PubMed

Adamson, S J; Sellman, J D

1998-06-01

Sixty-four patients on the Christchurch Methadone Treatment Programme waiting list were questioned on their drug-use behaviour, criminal activity and sources of income, both legal and illegal, for the preceding 7 days. Opioids used included morphine sulphate tablets, methadone and opium poppies, while other drugs used included tranquillizers, cannabis and alcohol. A significant minority were prescribed opioids. The mean cost of drugs used in 7 days across all subjects was 882 dollars. The mean financial gain from criminal sources for the same period was 1079 dollars and was derived from drug-related crime, property crime and prostitution. Few gender differences were found relating to criminal activity or drug use. The majority of the sample were on unemployment benefits of varying types while a minority were in paid employment. Those in paid employment did not earn significantly less from criminal activity, nor did they spend significantly less on drug use than did those not in paid employment. An important implication of these findings is that untreated opioid users are a substantial financial burden to the community, strongly supporting the argument for greater treatment provision.
Illegal drugs, anti-drug policy failure, and the need for institutional reforms in Colombia.

PubMed

Thoumi, Francisco E

2012-01-01

This paper is inspired by two anomalies encountered in the study of the illegal drugs industry. First, despite the very high profits of coca/cocaine and poppy/opium/heroin production, most countries that can produce do not. Why, for example, does Colombia face much greater competition in the international coffee, banana, and other legal product markets than in cocaine? And second, though illegal drugs are clearly associated with violence, why is it that illegal drug trafficking organizations have been so much more violent in Colombia and Mexico than in the rest of the world? The answers to these questions cannot be found in factors external to Colombia (and Mexico). They require identifying the societal weaknesses of each country. To do so, the history of the illegal drugs industry is surveyed, a simple model of human behavior that stresses the conflict between formal (legal) and informal (socially accepted) norms as a source of the weaknesses that make societies vulnerable is formulated. The reasons why there is a wide gap between formal and informal norms in Colombia are explored and the effectiveness of anti-drug policies is considered to explain why they fail to achieve their posited goals. The essay ends with reflections and conclusion on the need for institutional change.
Optimized ultrasound-assisted extraction procedure for the analysis of opium alkaloids in papaver plants by cyclodextrin-modified capillary electrophoresis.

PubMed

Fakhari, Ali Reza; Nojavan, Saeed; Ebrahimi, Samad Nejad; Evenhuis, Christopher John

2010-07-01

This study investigated the use of ultrasound-assisted extraction to improve the extraction efficiency of morphine, codeine and thebaine from the papaver plants. Extraction conditions such as type of solvent, temperature, duration, frequency and power level of ultrasonic were optimized and the influences of different parameters on resolution of alkaloids in CE were studied. The optimized condition for CE separation includes a sodium phosphate buffer (100 mM, pH 3.0) containing 5 mM alpha-CD. The optimized extraction conditions for ultrasound-assisted extraction was an extraction time of 1 h, an ultrasonic frequency of 60 kHz with water-methanol (80:20) at 40 degrees C as the extraction solvent. The LOD for alkaloids was found to be 0.1 microg/mL at a signal-to-noise ratio of 3:1. The RSDs for peak areas were in the range of 1.4-4.4%. The amounts of opium alkaloids (mg/100 g dried sample) in four Iranian papaver plants were found to be in the range of 7.8-8.7 (morphine), 5.5-9.5 (codeine) and 1.4-10.4 (thebaine). It should be emphasized that no cleanup of the filtered extract was required; hence, direct determination after extraction drastically simplifies the analytical process.
Environmentally Clean Mitigation of Undesirable Plant Life Using Lasers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubenchik, A M; McGrann, T J; Yamamoto, R M

This concept comprises a method for environmentally clean destruction of undesirable plant life using visible or infrared radiation. We believe that during the blossom stage, plant life is very sensitive to electromagnetic radiation, with an enhanced sensitivity to specific spectral ranges. Small doses of irradiation can arrest further plant growth, cause flower destruction or promote plant death. Surrounding plants, which are not in the blossoming stage, should not be affected. Our proposed mechanism to initiate this effect is radiation produced by a laser. Tender parts of the blossom possess enhanced absorptivity in some spectral ranges. This absorption can increase themore » local tissue temperature by several degrees, which is sufficient to induce bio-tissue damage. In some instances, the radiation may actually stimulate plant growth, as an alternative for use in increased crop production. This would be dependent on factors such as plant type, the wavelength of the laser radiation being used and the amount of the radiation dose. Practical, economically viable realization of this concept is possible today with the advent of high efficiency, compact and powerful laser diodes. The laser diodes provide an efficient, environmentally clean source of radiation at a variety of power levels and radiation wavelengths. Figure 1 shows the overall concept, with the laser diodes mounted on a movable platform, traversing and directing the laser radiation over a field of opium poppies.« less
Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol).

PubMed

Huda, S N; Grantham-McGregor, S M; Tomkins, A

2001-01-01

Iodine supplementation before pregnancy in iodine-deficient women prevents cretinism and neuromotor deficits in their offspring. It is unclear whether iodine supplementation benefits cognitive function in iodine-deficient school-aged children. We therefore conducted a double-blind, randomized, controlled trial of the effects of iodized poppy seed oil (Lipiodol) on cognitive and motor function and weight gain of iodine-deficient school children. The study was conducted with 305 children in grades 1 and 2 from 10 primary schools in two iodine-deficient areas in Bangladesh. The children were stratified by school and grade and randomly assigned to receive 400 mg of oral Lipiodol or a placebo. All children were given a battery of cognitive and motor function tests and had their weights, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) and urinary iodine levels measured before and 4 mo after the intervention. On enrollment, both groups were moderately iodine deficient (median urinary iodine values: placebo group = 3.3 micromol/L, n = 148; iodine group = 3.1 micromol/L, n = 152; goiter prevalence in both groups >95%). However, their T4 and TSH levels were within the normal range. After 4 mo, there was a significant treatment effect on urinary iodine levels (P < 0.0001), but the levels of the treated group were still below normal (median = 7.9 micromol/L). No significant differences were found in T4 and TSH levels, weight gain, cognitive or motor function. The findings suggest that Lipiodol supplementation in moderately iodine-deficient children with normal T4 levels is unlikely to benefit their cognitive function. However, it remains possible that other iodine preparations may have benefits.
21 CFR 1312.13 - Issuance of import permit.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., poppy straw and concentrate of poppy straw) having as its source: (1) Turkey, (2) India, (3) Spain, (4... material imported into the United States shall have as its original source Turkey and India. Except under...
21 CFR 1312.13 - Issuance of import permit.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., poppy straw and concentrate of poppy straw) having as its source: (1) Turkey, (2) India, (3) Spain, (4... material imported into the United States shall have as its original source Turkey and India. Except under...
21 CFR 1312.13 - Issuance of import permit.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., poppy straw and concentrate of poppy straw) having as its source: (1) Turkey, (2) India, (3) Spain, (4... material imported into the United States shall have as its original source Turkey and India. Except under...
21 CFR 1312.13 - Issuance of import permit.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., poppy straw and concentrate of poppy straw) having as its source: (1) Turkey, (2) India, (3) Spain, (4... material imported into the United States shall have as its original source Turkey and India. Except under...
21 CFR 1312.13 - Issuance of import permit.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., poppy straw and concentrate of poppy straw) having as its source: (1) Turkey, (2) India, (3) Spain, (4... material imported into the United States shall have as its original source Turkey and India. Except under...
Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study.

PubMed

Lee, Franklin C; Holt, Sarah K; Hsi, Ryan S; Haynes, Brandon M; Harper, Jonathan D

2017-02-01

To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intraoperatively, in the recovery unit, and at home was recorded. Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and "high-pain" measure (P = .02) CONCLUSION: B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits. Copyright © 2016 Elsevier Inc. All rights reserved.
Preoperative Belladonna and Opium Suppository for Ureteral Stent Pain: A Randomized, Double-blinded, Placebo-controlled Study

PubMed Central

Lee, Franklin C.; Holt, Sarah K.; Hsi, Ryan S.; Haynes, Brandon M.; Harper, Jonathan D.

2017-01-01

OBJECTIVE To investigate whether the use of a belladonna and opium (B&O) rectal suppository administered immediately before ureteroscopy (URS) and stent placement could reduce stent-related discomfort. METHODS A randomized, double-blinded, placebo-controlled study was performed from August 2013 to December 2014. Seventy-one subjects were enrolled and randomized to receive a B&O (15 mg/30 mg) or a placebo suppository after induction of general anesthesia immediately before URS and stent placement. Baseline urinary symptoms were assessed using the American Urological Association Symptom Score (AUASS). The Ureteral Stent Symptom Questionnaire and AUASS were completed on postoperative days (POD) 1, 3, and after stent removal. Analgesic use intra-operatively, in the recovery unit, and at home was recorded. RESULTS Of the 71 subjects, 65 had treatment for ureteral (41%) and renal (61%) calculi, 4 for renal urothelial carcinoma, and 2 were excluded for no stent placed. By POD3, the B&O group reported a higher mean global quality of life (QOL) score (P = .04), a better mean quality of work score (P = .05), and less pain with urination (P = .03). The B&O group reported an improved AUASS QOL when comparing POD1 with post-stent removal (P = .04). There was no difference in analgesic use among groups (P = .67). There were no episodes of urinary retention. Age was associated with unplanned emergency visits (P <.00) and “high-pain” measure (P = .02) CONCLUSION B&O suppository administered preoperatively improved QOL measures and reduced urinary-related pain after URS with stent. Younger age was associated with severe stent pain and unplanned hospital visits. PMID:27658661
77 FR 2321 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

..., poppy straw, concentrate of poppy straw, and coca leaves. As explained in the Correction to Notice of... schedule I or II, which fall under the authority of section 1002(a)(2)(B) of the Act 21 U.S.C. 952(a)(2)(B...
75 FR 69459 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-12

..., poppy straw, concentrate of poppy straw, and coca leaves. As explained in the Correction to Notice of... schedule I or II, which fall under the authority of section 1002(a)(2)(B) of the Act [(21 U.S.C. 952 (a)(2...
Forest conflict in Thailand: northern minorities in focus.

PubMed

Hares, Minna

2009-03-01

This paper aims at exploring the local background of and solutions to the forest conflict in upland areas inhabited by ethnic minorities, who are called hill tribes, in northern Thailand. A so-called hill tribe problem has been officially identified as a result of the slash-and-burn cultivation and other perceived problems, such as opium poppy cultivation, illegal immigration, and the suspicion of disloyalty to the state. This has created distrust and tension between the groups and authorities. The local conflict has recently been related to the dilemma of conserving the forest from all human interference, while many people live and make their livelihood within and adjacent to the protected areas. Furthermore, as the results imply, strictly protected areas and reforestation have also increased the competition over land and natural resources and, thereby, the likelihood of local conflicts. The scarcity and pollution of water, illegal logging, and poor fire control have contributed to the conflicts between local communities. The conflicts between the local communities and officials have been nourished by political and public discussions. Using definitions and terms with negative connotations and ignoring the heterogeneity between the groups or labeling some groups as malevolent have increased distrust and strengthened existing stereotypical images. Conflict resolution starts with efforts toward better mutual understanding, and changes in structures and attitudes are necessary. Local cooperation, utilization of traditional methods, and local institutions are central to conflict solving.
Forest plunder in Southeast Asia: an environmental security nexus in Burma and Cambodia.

PubMed

Talbott, K; Brown, M

1998-01-01

This article discusses the cycle of conversion, consumption, and corruption that undermines the environment and civil society in Cambodia and Burma (Myanmar). In these countries, forests are declining in patterns similar to other Southeast Asian deforestation. Illegal logging, prostitution, and heroin trafficking constitute the bulk of Cambodia's shadow economy. Revenues are used to provide financial support for political causes and build the private wealth of the elite. Major political and guerilla groups and the Cambodian military have been major beneficiaries of logging revenue, supported private sector forestry in many military zones, and facilitated logging and trade. About 40% of land goes to forest concessions granted to Southeast Asian companies, and revenues bypass the regular state budget. In Burma, the cease fire agreements in the early 1990s, led to remote border area forests being opened up to large, nonsustainable commercial timber mining. Land was divided into ethnic and government controlled areas. Timber profits were funneled into a business owned by members of the new ruling force, the SLORC, and used to launder drug exports and profits. Trading partners include Thailand, and most recently, China. It is speculated that deforested areas are replanted with opium poppies, and trade routes carry timber and heroin. The unregulated logging industry and the lack of financial accounting of the timber trade undermine the structures of civil society and good governance. Forest policies appear progressive but are in reality unenforced. Politics and agreements in both countries are closely tied to deforestation issues.

Forest Conflict in Thailand: Northern Minorities in Focus

NASA Astrophysics Data System (ADS)

Hares, Minna

2009-03-01

This paper aims at exploring the local background of and solutions to the forest conflict in upland areas inhabited by ethnic minorities, who are called hill tribes, in northern Thailand. A so-called hill tribe problem has been officially identified as a result of the slash-and-burn cultivation and other perceived problems, such as opium poppy cultivation, illegal immigration, and the suspicion of disloyalty to the state. This has created distrust and tension between the groups and authorities. The local conflict has recently been related to the dilemma of conserving the forest from all human interference, while many people live and make their livelihood within and adjacent to the protected areas. Furthermore, as the results imply, strictly protected areas and reforestation have also increased the competition over land and natural resources and, thereby, the likelihood of local conflicts. The scarcity and pollution of water, illegal logging, and poor fire control have contributed to the conflicts between local communities. The conflicts between the local communities and officials have been nourished by political and public discussions. Using definitions and terms with negative connotations and ignoring the heterogeneity between the groups or labeling some groups as malevolent have increased distrust and strengthened existing stereotypical images. Conflict resolution starts with efforts toward better mutual understanding, and changes in structures and attitudes are necessary. Local cooperation, utilization of traditional methods, and local institutions are central to conflict solving.
The Narcotics Emirate of Afghanistan: Armed Polities and Their Roles in Illicit Drug Production and Conflict 1980-2010

DTIC Science & Technology

2010-12-01

yields in 1969 and 1970.78 American and European smugglers facilitated the movement of Afghan hash throughout the world until U.S. drug enforcement...significantly affected opium yields . *Denotes approximation from UNDCP records. Table 4. Sampling of Opium Production (metric tons) According to the...shorter grow-cycle than food crops like wheat, allowing farmers to double-crop with livestock fodder, such as maize following the opium harvest
26 CFR 301.7641-1 - Supervision of operations of certain manufacturers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... opium suitable for smoking purposes, see subparts E, F, G, and H or part 45 of this chapter (Miscellaneous Stamp Tax Regulations). For regulations relating to the manufacture of opium suitable for smoking...
26 CFR 301.7641-1 - Supervision of operations of certain manufacturers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... opium suitable for smoking purposes, see subparts E, F, G, and H or part 45 of this chapter (Miscellaneous Stamp Tax Regulations). For regulations relating to the manufacture of opium suitable for smoking...
26 CFR 301.7641-1 - Supervision of operations of certain manufacturers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... opium suitable for smoking purposes, see subparts E, F, G, and H or part 45 of this chapter (Miscellaneous Stamp Tax Regulations). For regulations relating to the manufacture of opium suitable for smoking...
26 CFR 301.7641-1 - Supervision of operations of certain manufacturers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... opium suitable for smoking purposes, see subparts E, F, G, and H or part 45 of this chapter (Miscellaneous Stamp Tax Regulations). For regulations relating to the manufacture of opium suitable for smoking...
26 CFR 301.7641-1 - Supervision of operations of certain manufacturers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... opium suitable for smoking purposes, see subparts E, F, G, and H or part 45 of this chapter (Miscellaneous Stamp Tax Regulations). For regulations relating to the manufacture of opium suitable for smoking...
Examining the debate on the use of medical marijuana.

PubMed

DuPont, R L

1999-01-01

The opium poppy and the coca leaf offer useful perspectives on the current controversies over medical marijuana. In both cases, purified synthetic analogues of biologically active components of ancient folk remedies have become medical mainstays without undermining efforts to reduce nonmedical drug use. A decade ago, a campaign strove to legalize heroin for the compassionate treatment of pain in terminally ill patients. Like the current campaign to legalize medical marijuana, many well-meaning people supported this effort. The campaign for medical heroin was stopped by science when double-blind studies showed that heroin offered no benefits over the standard opioid analgesics in the treatment of severe cancer pain. Scientific medicine requires purified chemicals in carefully controlled doses without contaminating toxic substances. That a doctor would one day write a prescription for leaves to be burned is unimaginable. The Controlled Substances Act and international treaties limit the use of abused drugs or medicines. In contrast to smoked marijuana, specific chemicals in marijuana or, more likely, synthetic analogues, may prove to be of benefit to some patients with specific illnesses. Most opponents of medical use of smoked marijuana are not hostile to the medical use of purified synthetic analogues or even synthetic tetrahydrocannabinol (THC), which has been available in the United States for prescription by any licensed doctor since 1985. In contrast, most supporters of smoked marijuana are hostile to the use of purified chemicals from marijuana, insisting that only smoked marijuana leaves be used as "medicine," revealing clearly that their motivation is not scientific medicine but the back door legalization of marijuana.
Mycobiota and mycotoxins in bee pollen collected from different areas of Slovakia.

PubMed

Kačániová, Miroslava; Juráček, Miroslav; Chlebo, Róbert; Kňazovická, Vladimíra; Kadasi-Horáková, Miriam; Kunová, Simona; Lejková, Jadža; Haščík, Peter; Mareček, Ján; Simko, Milan

2011-01-01

Contamination by microscopic fungi and mycotoxins in different bee pollen samples, which were stored under three different ways of storing as freezing, drying and UV radiation, was investigated. During spring 2009, 45 samples of bee-collected pollen were gathered from beekeepers who placed their bee colonies on monocultures of sunflower, rape and poppy fields within their flying distance. Bee pollen was collected from bees' legs by special devices placed at the entrance to hives. Samples were examined for the concentration and identification of microscopic fungi able to grow on Malt and Czapek-Dox agar and mycotoxins content [deoxynivalenol (DON), T-2 toxin (T-2), zearalenone (ZON) and total aflatoxins (AFL), fumonisins (FUM), ochratoxins (OTA)] by direct competitive enzyme-linked immunosorbent assays (ELISA). The total number of microscopic fungi in this study ranged from 2.98 ± 0.02 in frozen sunflower bee pollen to 4.06 ± 0.10 log cfu.g(-1) in sunflower bee pollen after UV radiation. In this study, 449 isolates belonging to 21 fungal species representing 9 genera were found in 45 samples of bee pollen. The total isolates were detected in frozen poppy pollen 29, rape pollen 40, sunflower pollen 80, in dried poppy pollen 12, rape pollen 36, sunflower 78, in poppy pollen after UV radiation treatment 54, rape 59 and sunflower 58. The most frequent isolates of microscopic fungi found in bee pollen samples of all prevalent species were Mucor mucedo (49 isolates), Alternaria alternata (40 isolates), Mucor hiemalis (40 isolates), Aspergillus fumigatus (33 isolates) and Cladosporium cladosporioides (31 isolates). The most frequently found isolates were detected in sunflower bee pollen frozen (80 isolates) and the lowest number of isolates was observed in poppy bee pollen dried (12 isolates). The most prevalent mycotoxin of poppy bee pollen was ZON (361.55 ± 0.26 μg.kg(-1)), in rape bee pollen T-2 toxin (265.40 ± 0.18 μg.kg(-1)) and in sunflower bee pollen T-2 toxin
Noscapine induces mitochondria-mediated apoptosis in human colon cancer cells in vivo and in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Zi-Rong; Liu, Meng; Peng, Xiu-Lan

2012-05-11

Highlights: Black-Right-Pointing-Pointer Noscapine inhibited cell viability of colon cancer in a time- and dose- dependent manner. Black-Right-Pointing-Pointer G{sub 2}/M phase arrest and chromatin condensation and nuclear fragmentation were induced. Black-Right-Pointing-Pointer Noscapine promoted apoptosis via mitochondrial pathways. Black-Right-Pointing-Pointer Tumorigenicity was inhibited by noscapine. -- Abstract: Noscapine, a phthalide isoquinoline alkaloid derived from opium, has been widely used as a cough suppressant for decades. Noscapine has recently been shown to potentiate the anti-cancer effects of several therapies by inducing apoptosis in various malignant cells without any detectable toxicity in cells or tissues. However, the mechanism by which noscapine induces apoptosis in colonmore » cancer cells remains unclear. The signaling pathways by which noscapine induces apoptosis were investigated in colon cancer cell lines treated with various noscapine concentrations for 72 h, and a dose-dependent inhibition of cell viability was observed. Noscapine effectively inhibited the proliferation of LoVo cells in vitro (IC{sub 50} = 75 {mu}M). This cytotoxicity was reflected by cell cycle arrest at G{sub 2}/M and subsequent apoptosis, as indicated by increased chromatin condensation and fragmentation, the upregulation of Bax and cytochrome c (Cyt-c), the downregulation of survivin and Bcl-2, and the activation of caspase-3 and caspase-9. Moreover, in a xenograft tumor model in mice, noscapine injection clearly inhibited tumor growth via the induction of apoptosis, which was demonstrated using a TUNEL assay. These results suggest that noscapine induces apoptosis in colon cancer cells via mitochondrial pathways. Noscapine may be a safe and effective chemotherapeutic agent for the treatment of human colon cancer.« less
Sociocultural diversity and substance use pattern in Arunachal Pradesh, India.

PubMed

Chaturvedi, H K; Mahanta, J

2004-04-09

An epidemiological study on substance use was carried out to assess the prevalence and pattern of tobacco, alcohol, and opium being used commonly in ethnographic diverse population of Arunachal Pradesh, India. Representative sample of 5135 people age > or =10 years were interviewed to collect information about their habit of substance use. Over all, prevalence of substance use was 30.9% tobacco (22.8% chewers and 12.1% smokers), 30% alcohol, and 4.8% opium, which vary across location, gender, race, age, education, and occupation. Though tobacco and alcohol was commonly used among all the tribes, but high alcohol use among Tangsa and Tutsa tribes reflects strong cultural belief. Religiously, opium use was low among Christian and Hindu at lower (< 1000 m) altitude, but high among Buddhist, Indigenous, and Hindu living at higher altitude. Among males, high multivariate rate ratio of opium users was seen among the population of high altitude (9.1). Moreover, it was also high among Singpho (7.1) and Khamti (9.7) tribes living in low altitude area, which shows the strong geo-ethnographic influence. Average age at initiation of alcohol use (12.4 years) was significantly lower than tobacco (17.6 years), and opium (23.3 years) indicate social acceptability of alcohol drinking at early age. Use of multiple substances and high prevalence of opium express the alarming situation of substance misuse in the region. Besides few limitations, varied results of socio-cultural and ethnic influences recalls integrated approach to break the traditional belief associated with alcohol and drug abuse from the society.
Microbe associated molecular patterns from rhizosphere bacteria trigger germination and Papaver somniferum metabolism under greenhouse conditions.

PubMed

Bonilla, A; Sarria, A L F; Algar, E; Muñoz Ledesma, F J; Ramos Solano, B; Fernandes, J B; Gutierrez Mañero, F J

2014-01-01

Ten PGPR from different backgrounds were assayed on Papaver somniferum var. Madrigal to evaluate their potential as biotic elicitors to increase alkaloid content under the rationale that some microbe associated molecular patterns (MAMPs) are able to trigger plant metabolism. First, the 10 strains and their culture media at two different concentrations were tested for their ability to trigger seed germination. Then, the best three strains were tested for their ability to increase seedling growth and alkaloid levels under greenhouse conditions. Only three strains and their culture media enhanced germination. Then, germination enhancing capacity of these best three strains, N5.18 Stenotrophomonas maltophilia, Aur9 Chryseobacterium balustinum and N21.4 Pseudomonas fluorescens was evaluated in soil. Finally, the three strains were applied on seedlings at two time points, by soil drench or by foliar spray. Photosynthesis was measured, plant height was recorded, capsules were weighted and alkaloids analyzed by HPLC. Only N5.18 delivered by foliar spray significantly increased plant height coupled to an increase in total alkaloids and a significant increase in opium poppy straw dry weight; these increases were supported by a better photosynthetic efficiency. The relative contents of morphine, thebaine, codeine and oripavine were affected by this treatment causing a significant increase in morphine coupled to a decrease in thebaine, demonstrating the effectivity of MAMPs from N5.18 in this plant species. Considering the increase in capsule biomass and alkaloids together with the acceleration of germination, strain N5.18 appears as a good candidate to elicit plant metabolism and consequently, to increase productivity of Papaver somniferum. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
The ethnobotany of psychoactive plant use: a phylogenetic perspective

PubMed Central

2016-01-01

Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests
The ethnobotany of psychoactive plant use: a phylogenetic perspective.

PubMed

Alrashedy, Nashmiah Aid; Molina, Jeanmaire

2016-01-01

Psychoactive plants contain chemicals that presumably evolved as allelochemicals but target certain neuronal receptors when consumed by humans, altering perception, emotion and cognition. These plants have been used since ancient times as medicines and in the context of religious rituals for their various psychoactive effects (e.g., as hallucinogens, stimulants, sedatives). The ubiquity of psychoactive plants in various cultures motivates investigation of the commonalities among these plants, in which a phylogenetic framework may be insightful. A phylogeny of culturally diverse psychoactive plant taxa was constructed with their psychotropic effects and affected neurotransmitter systems mapped on the phylogeny. The phylogenetic distribution shows multiple evolutionary origins of psychoactive families. The plant families Myristicaceae (e.g., nutmeg), Papaveraceae (opium poppy), Cactaceae (peyote), Convolvulaceae (morning glory), Solanaceae (tobacco), Lamiaceae (mints), Apocynaceae (dogbane) have a disproportionate number of psychoactive genera with various indigenous groups using geographically disparate members of these plant families for the same psychoactive effect, an example of cultural convergence. Pharmacological traits related to hallucinogenic and sedative potential are phylogenetically conserved within families. Unrelated families that exert similar psychoactive effects also modulate similar neurotransmitter systems (i.e., mechanistic convergence). However, pharmacological mechanisms for stimulant effects were varied even within families suggesting that stimulant chemicals may be more evolutionarily labile than those associated with hallucinogenic and sedative effects. Chemically similar psychoactive chemicals may also exist in phylogenetically unrelated lineages, suggesting convergent evolution or differential gene regulation of a common metabolic pathway. Our study has shown that phylogenetic analysis of traditionally used psychoactive plants suggests
Drug Trafficking and North Korea: Issues for U.S. Policy

DTIC Science & Technology

2007-01-25

Government is involved in manufacturing and trafficking in illegal drugs.”3 The provisions of the Foreign Assistance Act of 1961 referred to above require...probably manufacture methamphetamine drugs.13 The Department of State’s March 2006 International Narcotics Control Strategy Report (INCSR) notes...government cultivates opium illicitly, refines opium into heroin, and manufactures methamphetamine drugs in North Korea as a state-organized and
Endogenous Morphine in SH-SY5Y Cells and the Mouse Cerebellum

PubMed Central

Taleb, Omar; Kemmel, Véronique; Laux, Alexis; Miehe, Monique; Delalande, François; Roussel, Guy; Van Dorsselaer, Alain; Metz-Boutigue, Marie-Hélène; Aunis, Dominique; Goumon, Yannick

2008-01-01

Background Morphine, the principal active agent in opium, is not restricted to plants, but is also present in different animal tissues and cell types, including the mammalian brain. In fact, its biosynthetic pathway has been elucidated in a human neural cell line. These data suggest a role for morphine in brain physiology (e.g., neurotransmission), but this hypothesis remains a matter of debate. Recently, using the adrenal neuroendocrine chromaffin cell model, we have shown the presence of morphine-6-glucuronide (M6G) in secretory granules and their secretion products, leading us to propose that these endogenous alkaloids might represent new neuroendocrine factors. Here, we investigate the potential function of endogenous alkaloids in the central nervous system. Methodology and Principal Findings Microscopy, molecular biology, electrophysiology, and proteomic tools were applied to human neuroblastoma SH-SY5Y cells (i) to characterize morphine and M6G, and (ii) to demonstrate the presence of the UDP-glucuronyltransferase 2B7 enzyme, which is responsible for the formation of M6G from morphine. We show that morphine is secreted in response to nicotine stimulation via a Ca2+-dependent mechanism involving specific storage and release mechanisms. We also show that morphine and M6G at concentrations as low as 10−10 M are able to evoke specific naloxone-reversible membrane currents, indicating possible autocrine/paracrine regulation in SH-SY5Y cells. Microscopy and proteomic approaches were employed to detect and quantify endogenous morphine in the mouse brain. Morphine is present in the hippocampus, cortex, olfactory bulb, and cerebellum at concentration ranging from 1.45 to 7.5 pmol/g. In the cerebellum, morphine immunoreactivity is localized to GABA basket cells and their termini, which form close contacts on Purkinje cell bodies. Conclusions/Significance The presence of morphine in the brain and its localization in particular areas lead us to conclude that it has a
Insanity: Four Decades of U.S. Counterdrug Strategy (Carlisle Paper)

DTIC Science & Technology

2012-12-01

provide pleasure.3 By the early-1800s, a burgeoning patent medicine industry advertised preparations containing large quantities of opium;4 in 1844...Congress passed the Pure Food and Drug Act, which effectively eliminated cocaine and opium from all patent medicines and soft drinks by requiring accurate...www.vanityfair.com/politics/features/2009/07/drug-czars- slideshow200907#slide=1. 49. In March 1972, Nixon created the National Commission on Marihuana and
Profile of narcotic abuse in peninsula Malaysia.

PubMed

Buhrich, N; Haq, S

1980-01-01

Demographic and drug abuse characteristics of 3,484 new drug abuse contacts presenting to the General Hospital, Kuala Lumpur, Malaysia are reported. The large majority were heroin inhalers. They were different from the traditional Eastern opium inhalers and similar to Western heroin injectors in that they were young, male, single, and frequently unemployed. These features and the relative underrepresentation of Chinese suggest that the Chinese of this study did not learn narcotic abuse from opium-smoking relatives.
Patterns of pre-treatment drug abuse, drug treatment history and characteristics of addicts in methadone maintenance treatment in Iran

PubMed Central

2012-01-01

Background Opiates are the main drugs of abuse, and Methadone Maintenance Treatment (MMT) is the most widely administered drug addiction treatment program in Iran. Our study aimed to investigate patterns of pre-treatment drug abuse, addiction treatment history and characteristics of patients in MMT in Tehran. Methods We applied a stratified cluster random sampling technique and conducted a cross-sectional survey utilizing a standard patient characteristic and addiction history form with patients (n = 810) in MMT. The Chi-square test and t-test served for statistical analyses. Results A clear majority of the participants were men (96%), more than 60% of whom were between 25 and 44 years of age, educated (89% had more than elementary education), and employed (>70%). The most commonly reported main drugs of abuse prior to MMT entry were opium (69%) and crystalline heroin (24%). The patients’ lifetime drug experience included opium (92%), crystalline heroin (28%), cannabis (16%), amphetamines (15%), and other drugs (33%). Crystalline heroin abusers were younger than opium users, had begun abusing drugs earlier, and reported a shorter history of opiate addiction. Conclusion Opium and crystalline heroin were the main drugs of abuse. A high rate of addiction using more dangerous opiate drugs such as crystalline heroin calls for more preventive efforts, especially among young men. PMID:22676557
[The opiate pharmacopeia in France from its origins to the 19th century].

PubMed

Warolin, Christian

2010-04-01

For thousands of years, opium was the main remedy against pain. Its analgesic properties have been known since antiquity, as well as its stupefacient, narcotic and addictive effects. A countless number of opiate galenical preparations had already been formulated by the beginning of our era. The best-known were electuaries, complex drugs combining multiple active substances, essentially plant-based, used to obtain beneficial effects for different aliments. These universal remedies were panaceas. Sonne opium--or opiate--based electuaries were recommended as antidotes to poison or snake venom. The best-known, Mithridate and Theriac Andromache (Venice Treacle), the latter also containing viper flesh, combined up to a hundred or so ingredients. However, this polypharmacy was criticized and it was an English doctor, Thomas Sydenham, to whom we owe the preparation of a liquid laudanum which was easier to administer than an electuary. Sydenham's laudanum (1683) was adopted by ail the pharmacopeias. Later, based on a traditional research approach, pharmacists attempted to isolate the active principles of opium. Seguin, but above ail the German pharmacist Sertürner (in 1805 and 1817) isolated morphine. Organic chemists took over from the analysts, and morphine derivatives were obtained by hemi-synthesis (heroin), and then central analgesics, or opioids, by total synthesis. Opium is no longer seen as the only supreme remedy for painful disorders, and its galenic forms have gradually disappeared from pharmacopeias.

76 FR 65749 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... treatment of wounds which contains trace amounts of the controlled substances normally found in poppy straw... the company's compliance with state and local laws, and a review of the company's background and...
49 CFR 40.139 - On what basis does the MRO verify test results for codeine and morphine?

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the... the case of other drugs (see § 40.137). Consumption of food products (e.g., poppy seeds) must not be...
49 CFR 40.139 - On what basis does the MRO verify test results for codeine and morphine?

Code of Federal Regulations, 2011 CFR

2011-10-01

... PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the... the case of other drugs (see § 40.137). Consumption of food products (e.g., poppy seeds) must not be...
Heroin

MedlinePlus

... DEA Museum and Visitors' Center National Prevention Week Heroin Last Updated: Wednesday, December 27, 2017 What is ... from morphine and extracted from certain poppy plants. Heroin comes in a white or brownish powder, or ...
Prescription Pain Relievers (Opiods)

MedlinePlus

... derived from poppy flowers or lab-made, semi-synthetic substitutes. They work by attaching to particular sites ... to the terms & conditions Related Drugs Fentanyl & Other Synthetic Opioids OxyContin Heroin Morphine Next Steps Medicine Abuse: ...
76 FR 30969 - Importer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-27

... treatment of wounds which contain trace amounts of the controlled substances normally found in poppy straw... company's background and history. Therefore, pursuant to 21 U.S.C. 952(a) and 958(a), and in accordance...
78 FR 69131 - Importer of Controlled Substances; Notice of Registration; Catalent CTS, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... treatment of wounds which contains trace amounts of the controlled substances normally found in poppy straw... company's background and history. Therefore, pursuant to 21 U.S.C. 952(a) and 958(a), and in accordance...
76 FR 62449 - Manufacturer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

...), this is notice that on May 4, 2011, Cambrex Charles City, Inc., 1205 11th Street, Charles City, Iowa... Concentrate of Poppy Straw (9670) II Sufentanil (9740) II Fentanyl (9801) II The company will manufacture the...
L-Tryptophan

MedlinePlus

... calamus, California poppy, catnip, hops, Jamaican dogwood, kava, St. John's wort, skullcap, valerian, yerba mansa, and others. ... 5-HTP, Hawaiian baby woodrose, and S-adenosylmethionine (SAMe).St. John's wortCombining L-tryptophan with St. John's wort ...
49 CFR 40.293 - What is the SAP's function in conducting the initial evaluation of an employee?

Code of Federal Regulations, 2013 CFR

2013-10-01

... violation of a DOT drug or alcohol regulation (e.g., related to assertions of use of hemp oil, “medical marijuana” use, “contact positives,” poppy seed ingestion, job stress); or (3) Personal opinions you may...
49 CFR 40.293 - What is the SAP's function in conducting the initial evaluation of an employee?

Code of Federal Regulations, 2014 CFR

2014-10-01

... violation of a DOT drug or alcohol regulation (e.g., related to assertions of use of hemp oil, “medical marijuana” use, “contact positives,” poppy seed ingestion, job stress); or (3) Personal opinions you may...
49 CFR 40.293 - What is the SAP's function in conducting the initial evaluation of an employee?

Code of Federal Regulations, 2011 CFR

2011-10-01

... violation of a DOT drug or alcohol regulation (e.g., related to assertions of use of hemp oil, “medical marijuana” use, “contact positives,” poppy seed ingestion, job stress); or (3) Personal opinions you may...
49 CFR 40.293 - What is the SAP's function in conducting the initial evaluation of an employee?

Code of Federal Regulations, 2012 CFR

2012-10-01

... violation of a DOT drug or alcohol regulation (e.g., related to assertions of use of hemp oil, “medical marijuana” use, “contact positives,” poppy seed ingestion, job stress); or (3) Personal opinions you may...
76 FR 81979 - Manufacturer of Controlled Substances; Notice of Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances... Cordova, California 95670, made application to the Drug Enforcement Administration (DEA) as a bulk manufacturer of the following basic classes of controlled substances: Drug Schedule Thebaine (9333) II Poppy...
National population size estimation of illicit drug users through the network scale-up method in 2013 in Iran.

PubMed

Nikfarjam, Ali; Shokoohi, Mostafa; Shahesmaeili, Armita; Haghdoost, Ali Akbar; Baneshi, Mohammad Reza; Haji-Maghsoudi, Saiedeh; Rastegari, Azam; Nasehi, Abbas Ali; Memaryan, Nadereh; Tarjoman, Termeh

2016-05-01

For a better understanding of the current situation of drug use in Iran, we utilized the network scale-up approach to estimate the prevalence of illicit drug use in the entire country. We implemented a self-administered, street-based questionnaire to 7535 passersby from the general public over 18 years of age by street based random walk quota sampling (based on gender, age and socio-economic status) from 31 provinces in Iran. The sample size in each province was approximately 400, ranging from 200 to 1000. In each province 75% of sample was recruited from the capital and the remaining 25% was recruited from one of the large cities of that province through stratified sampling. The questionnaire comprised questions on demographic information as well as questions to measure the total network size of participants as well as the network size in each of seven drug use groups including Opium, Shire (combination of Opium residue and pure opium), Crystal Methamphetamine, heroin/crack (which in Iranian context is a cocaine-free drug that mostly contains heroin, codeine, morphine and caffeine with or without other drugs), Hashish, Methamphetamine/LSD/ecstasy, and injecting drugs. The estimated size for each group was adjusted for transmission and barrier ratios. The most common type of illicit drug used was opium with the prevalence of 1500 per 100,000 population followed by shire (660), crystal methamphetamine (590), hashish (470), heroin/crack (350), methamphetamine, LSD and ecstasy (300) and injecting drugs (280). All types of substances were more common among men than women. The use of opium, shire and injecting drugs was more common in individuals over 30 whereas the use of stimulants and hashish was largest among individuals between 18 and 30 years of age. It seems that younger individuals and women are more desired to use new synthetic drugs such as crystal methamphetamine. Extending the preventive programs especially in youth as like as scaling up harm reduction
[Evaluation of spinal anesthesia blockade time with 0.5% hyperbaric bupivacaine, with or without sufentanil, in chronic opioid users: a randomized clinical trial].

PubMed

Sadeghi, Mostafa; Yekta, Reza Atef; Azimaraghi, Omid; Barzin, Gilda; Movafegh, Ali

2016-01-01

The primary outcome of this study was to evaluate the effect of adding sufentanil to hyperbaric bupivacaine on duration of sensory blockade of spinal anesthesia in chronic opioid users in comparison with non-addicts. Sixty patients scheduled for orthopedic surgery under spinal anesthesia were allocated into four groups: group 1 (no history of opium use who received intrathecal hyperbaric bupivacaine along with 1mL saline as placebo); group 2 (no history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5μg]); group 3 (positive history of opium use who received intrathecal bupivacaine along with 1mL saline as placebo) and group 4 (positive history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5μg]). The onset time and duration of sensory and motor blockade were measured. The duration of sensory blockade in group 3 was 120±23.1min which was significantly less than other groups (G1=148±28.7, G2=144±26.4, G4=139±24.7, p=0.007). The duration of motor blockade in group 3 was 145±30.0min which was significantly less than other groups (G1=164±36.0, G2=174±26.8, G4=174±24.9, p=0.03). Addition of 5μg intrathecal sufentanil to hyperbaric bupivacaine in chronic opioid users lengthened the sensory and motor duration of blockade to be equivalent to blockade measured in non-addicts. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Evaluation of spinal anesthesia blockade time with 0.5% hyperbaric bupivacaine, with or without sufentanil, in chronic opioid users: a randomized clinical trial.

PubMed

Sadeghi, Mostafa; Yekta, Reza Atef; Azimaraghi, Omid; Barzin, Gilda; Movafegh, Ali

2016-01-01

The primary outcome of this study was to evaluate the effect of adding sufentanil to hyperbaric bupivacaine on duration of sensory blockade of spinal anesthesia in chronic opioid users in comparison with non-addicts. Sixty patients scheduled for orthopedic surgery under spinal anesthesia were allocated into four groups: group 1 (no history of opium use who received intrathecal hyperbaric bupivacaine along with 1mL saline as placebo); group 2 (no history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5μg]); group 3 (positive history of opium use who received intrathecal bupivacaine along with 1mL saline as placebo) and group 4 (positive history of opium use who received intrathecal bupivacaine along with 1mL sufentanil [5μg]). The onset time and duration of sensory and motor blockade were measured. The duration of sensory blockade in group 3 was 120±23.1min which was significantly less than other groups (G1=148±28.7, G2=144±26.4, G4=139±24.7, p=0.007). The duration of motor blockade in group 3 was 145±30.0min which was significantly less than other groups (G1=164±36.0, G2=174±26.8, G4=174±24.9, p=0.03). Addition of 5μg intrathecal sufentanil to hyperbaric bupivacaine in chronic opioid users lengthened the sensory and motor duration of blockade to be equivalent to blockade measured in non-addicts. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Burma: the political economy of violence.

PubMed

Brown, C

1999-09-01

Protracted conflict and violence in Burma have been conducive to the growth of the opium industry, Burma's single financial success in recent years of economic crisis and authoritarian rule. This in turn has fed violence and subsequent humanitarian crisis. This paper argues that the underlying political economy of the conflict has been overlooked, while conflict itself has been treated as a peripheral factor in questions of 'development', and further that the opium dynamic is a vital factor in continued violence and vulnerability for non-combatants in the region. A political economy approach, identifying the beneficiaries of violence, will offer a more holistic and effective approach to the protracted crisis.
76 FR 51399 - Importer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-18

..., concentrate of poppy straw or coca leaves. As explained in the Correction to Notice of Application pertaining... schedule I or II, which fall under the authority of section 1002(a)(2)(B) of the Act (21 U.S.C. 952(a)(2)(B...
Effects of gluten-free breads, with varying functional supplements, on the biochemical parameters and antioxidant status of rat serum.

PubMed

Świeca, Michał; Reguła, Julita; Suliburska, Joanna; Złotek, Urszula; Gawlik-Dziki, Urszula

2015-09-01

This paper examines the effects of gluten-free bread enriched with functional ingredients (milk powder, poppy, sunflower and pumpkin seeds, egg yolk, carum, hazel nuts and amaranth) on the morphological and biochemical parameters and antioxidant status of rats serum. Rats were provided test diets--gluten-free breads and water ad libitum. After 14 days, the animals were weighed and killed. A hazel nut-amaranth bread diet significantly increased the level of thrombocytes when compared to control bread. A mixed bread diet significantly decreased cholesterol levels in rats. All fortified breads decreased triglyceride levels and alanine transaminase activity and caused an increase in antiradical activity of the serum. In rats fed with poppy-milk bread, milk-seed bread and mixed bread, a marked decrease in superoxide dismutase activity was found. Enriched breads reduced the levels of triglyceride and improved the antiradical properties of serum, although the physiological relevance of this needs to be confirmed by human studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

78 FR 64020 - Manufacturer of Controlled Substances, Notice of Registration, Siegfried USA, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

..., Notice of Registration, Siegfried USA, LLC The Notice dated July 23, 2013, and published in the Federal Register on August 1, 2013, 78 FR 46613, page 18338, Siegfried (USA), LLC., 33 Industrial Park Road...), and Poppy Straw Concentrate (9670). On August 6, 2013, Siegfried (USA), LLC., subsequently withdrew...
ARC-2010-ACD10-0059-008

NASA Image and Video Library

2010-04-14

Environmental sustainability is put into practice here in the native plant gardens that surround the main auditorium building at NASA Ames Research Center, Moffett Field, Calif. An assortment of the colors of the California poppy are shown in this image. The garden contains many other native plants as well.
49 CFR 40.139 - On what basis does the MRO verify test results involving opiates?

Code of Federal Regulations, 2014 CFR

2014-10-01

... FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the... legitimate medical explanation for the presence of the drug or drug metabolite in his or her system, as in the case of other drugs (see § 40.137). Consumption of food products (e.g., poppy seeds) must not be...
49 CFR 40.139 - On what basis does the MRO verify test results involving opiates?

Code of Federal Regulations, 2012 CFR

2012-10-01

... FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the... legitimate medical explanation for the presence of the drug or drug metabolite in his or her system, as in the case of other drugs (see § 40.137). Consumption of food products (e.g., poppy seeds) must not be...
49 CFR 40.139 - On what basis does the MRO verify test results involving opiates?

Code of Federal Regulations, 2013 CFR

2013-10-01

... FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Medical Review Officers and the... legitimate medical explanation for the presence of the drug or drug metabolite in his or her system, as in the case of other drugs (see § 40.137). Consumption of food products (e.g., poppy seeds) must not be...
Mexican Folkart for Children.

ERIC Educational Resources Information Center

Dominguez, Graciela; And Others

Directions, suggested materials, and illustrations are given for making paper mache pinatas and masks, cascarones, Ojos de Dios, maracas, dresser scarf embroidery, burlap murals, yarn designs, paper plate trays, paper cut designs, the poppy, sarape aprons, and paper Mexican dolls. Filled with candy and broken, the pinata is used on most Mexican…
Effectiveness of Coping Skills Education Program to Reduce Craving Beliefs among Addicts Referred To Addiction Centers in Hamadan: A Randomized Controlled Trial

PubMed Central

Ahmadpanah, Mohammad; Mirzaei Alavijeh, Mehdi; Allahverdipour, Hamid; Jalilian, Farzad; Haghighi, Mohammad; Afsar, Ali; Gharibnavaz, Hassan

2013-01-01

Abstract Background One of the most important factors affecting relapse of addiction is craving beliefs of substance use. The goal of the present study was assessment of the effectiveness of coping skills education program to reduce craving beliefs among opium addicts. Methods In a randomized controlled trial, during September 2011 to August 2012, 70 opium addicted men referred to the Behavioral Disorders and Substance Abuse Research Center in Hamadan, western Iran were assigned to intervention group (receiving coping skills education program) and control groups. The study information was analyzed using SPSS software. Results Regarding craving beliefs for continuing drug use, the two groups had similar scales at the beginning of interventional program, while the level of these beliefs was significantly reduced in the intervention group (P= 0.002), but not in the control group (P= 0.105). Also, a significant correlation was also revealed between taking advantage of the educational program and increase awareness of the signs of relapse in the intervention group (P=0.003) that was not revealed in the control (P= 0.174). On the other hand, executing coping skills education program led to reducecraving beliefs and improve knowledge towards signs of relapse. Conclusion Our findings demonstrate positive impact of coping skills education program after detoxification process on decrease of craving beliefs among opium addicts. PMID:26060622
Drug problem in southeast and southwest Asia.

PubMed

Kulsudjarit, Kongpetch

2004-10-01

In 2002, the drug problem in Southeast and Southwest Asia was serious, particularly in the production of opium and heroin in Afghanistan, Myanmar, and Laos, the three largest producers of illicit opium in the world. The increasing illicit manufacture of ATS, particularly methamphetamine, in Southeast Asia, mainly in China and Myanmar, was also a major concern. Some reports indicated that ephedrine, used for illicitly producing methamphetamine in Southeast Asia, is diverted and smuggled out of China and India, whereas caffeine, the adulterant used for producing methamphetamine tablets, is mainly smuggled into Myanmar through its border with Thailand. Seizure data showed a dramatic increase in trafficking in MDMA through Southeast Asia. In terms of the drug epidemic, in 2002, cannabis remained overall the main drug of abuse in all of the countries of Southeast and Southwest Asia. Opiates, mainly opium and heroin, were also the drugs of choice except in Thailand, where opiate abuse declined, but ATS was the main drug of abuse due to its low cost and availability. A significant increase in ATS abuse, amphetamine, methamphetamine, and MDMA among the youth who smoked, sniffed, and inhaled them was reported in Cambodia, China, Indonesia, Laos, Myanmar, the Philippines, and Thailand. Injecting drug use among opiate abusers has been identified as the prime cause of the rapid spread of HIV/AIDS in Southeast and Southwest Asia.
Metabolome analysis of 20 taxonomically related benzylisoquinoline alkaloid-producing plants.

PubMed

Hagel, Jillian M; Mandal, Rupasri; Han, Beomsoo; Han, Jun; Dinsmore, Donald R; Borchers, Christoph H; Wishart, David S; Facchini, Peter J

2015-09-15

Recent progress toward the elucidation of benzylisoquinoline alkaloid (BIA) metabolism has focused on a small number of model plant species. Current understanding of BIA metabolism in plants such as opium poppy, which accumulates important pharmacological agents such as codeine and morphine, has relied on a combination of genomics and metabolomics to facilitate gene discovery. Metabolomics studies provide important insight into the primary biochemical networks underpinning specialized metabolism, and serve as a key resource for metabolic engineering, gene discovery, and elucidation of governing regulatory mechanisms. Beyond model plants, few broad-scope metabolomics reports are available for the vast number of plant species known to produce an estimated 2500 structurally diverse BIAs, many of which exhibit promising medicinal properties. We applied a multi-platform approach incorporating four different analytical methods to examine 20 non-model, BIA-accumulating plant species. Plants representing four families in the Ranunculales were chosen based on reported BIA content, taxonomic distribution and importance in modern/traditional medicine. One-dimensional (1)H NMR-based profiling quantified 91 metabolites and revealed significant species- and tissue-specific variation in sugar, amino acid and organic acid content. Mono- and disaccharide sugars were generally lower in roots and rhizomes compared with stems, and a variety of metabolites distinguished callus tissue from intact plant organs. Direct flow infusion tandem mass spectrometry provided a broad survey of 110 lipid derivatives including phosphatidylcholines and acylcarnitines, and high-performance liquid chromatography coupled with UV detection quantified 15 phenolic compounds including flavonoids, benzoic acid derivatives and hydroxycinnamic acids. Ultra-performance liquid chromatography coupled with high-resolution Fourier transform mass spectrometry generated extensive mass lists for all species, which were
Light microscopy can reveal the consumption of a mixture of psychotropic plant and fungal material in suspicious death.

PubMed

Wiltshire, Patricia E J; Hawksworth, David L; Edwards, Kevin J

2015-08-01

Light microscopical examination of plant and fungal remains in the post mortem gut may be capable of demonstrating the ingestion of unexpected natural psychotropic materials. This is demonstrated here in a case in which a 'shaman' was accused of causing the death of a young man. The deceased had participated in a ceremony which involved the drinking of ayahuasca in order to induce a psychotropic experience. Ayahuasca is an infusion of Banisteriopsis caapi (ayahuasca vine), which produces a monoamine oxidase inhibitor, and one or more additional tropical plants, generally Psychotria viridis (chacruna) which produces dimethyltryptamine (DMT). The monoamine oxidase inhibitor prevents DMT from being broken down in the gut, so enabling its passage into the bloodstream and across the blood/brain barrier. Toxicological tests for DMT demonstrated the presence of this compound in the body. The deceased was reported to be in the habit of using Psilocybe semilanceata (liberty cap). This fungus (popularly called magic mushroom) contains psilocybin which is hydrolysed in the gut to psilocin; this compound mimics a serotonin uptake inhibitor, and also invokes psychotropic experiences. Microscopical examination established that the ileum and colon contained spores of Psilocybe and, in addition, pollen of Cannabis sativa and seeds of Papaver cf. somniferum (opium poppy). Both the plant species yield psychotropic substances. Palynological and mycological analysis of containers from the deceased person's dwelling also yielded abundant trace evidence of pertinent pollen and spores. The police had requested analysis for DMT but there was no screening for other psychotropic substances. Investigators were surprised that a mixture of hallucinogenic materials had been consumed by the deceased. The charge was modified from manslaughter to possession of a 'Class A' drug as the deceased had been consuming psychotropic substances not administered by the 'shaman'. Where death involving drugs
Characterization of third-body media particles and their effect on in vitro composite wear

PubMed Central

Lawson, Nathaniel C.; Cakir, Deniz; Beck, Preston; Litaker, Mark S.; Burgess, John O.

2012-01-01

Objectives The purpose of this study was to compare four medium particles currently used for in vitro composite wear testing (glass and PMMA beads and millet and poppy seeds). Methods Particles were prepared as described in previous wear studies. Hardness of medium particles was measured with a nano-indentor, particle size was measured with a particle size analyzer, and the particle form was determined with light microscopy and image analysis software. Composite wear was measured using each type of medium and water in the Alabama wear testing device. Four dental composites were compared: a hybrid (Z100), flowable microhybrid (Estelite Flow Quick), micromatrix (Esthet-X), and nano-filled (Filtek Supreme Plus). The test ran for 100,000 cycles at 1.2Hz with 70N force by a steel antagonist. Volumetric wear was measured by non-contact profilometry. A two-way analysis of variance (ANOVA) and Tukey's test was used to compare both materials and media. Results Hardness values (GPa) of the particles are (glass, millet, PMMA, poppy respectively): 1.310(0.150), 0.279(.170), 0.279(0.095), and 0.226(0.146). Average particle sizes (μm) are (glass, millet, PMMA, poppy respectively): 88.35(8.24), 8.07(4.05), 28.95(8.74), and 14.08(7.20). Glass and PMMA beads were considerably more round than the seeds. During composite wear testing, glass was the only medium that produced more wear than the use of water alone. The rank ordering of the materials varied with each medium, however, the glass and PMMA bead medium allowed better discrimination between materials. Significance PMMA beads are a practical and relevant choice for composite wear testing because they demonstrate similar physical properties as seeds but reduce the variability of wear measurements. PMID:22578990
Opioid Abuse and Addiction

MedlinePlus

Opioids, sometimes called narcotics, are a type of drug. They include strong prescription pain relievers, such as ... tramadol. The illegal drug heroin is also an opioid. Some opioids are made from the opium plant, ...
My General Education: "'Discovering" Amitav Ghosh

ERIC Educational Resources Information Center

Richards, Sandra L.

2015-01-01

Asked to recommend a faculty reading that might counteract our habits of overspecialization, I nominate Amitav Ghosh's "Sea of Poppies" (2008), the first novel in his "Ibis" trilogy. Reading Ghosh has offered me not only a fascinating introduction to the Indian Ocean world but also an occasion to reflect upon the dynamics of a…
La Artesania Mexicana (Mexican Handicrafts).

ERIC Educational Resources Information Center

Steele, Bettina

This booklet contains instructions in English and Spanish for making eleven typical Mexican craft articles. The instructions are accompanied by pen-and-ink drawings. The objects are (1) "La Rosa" (The Rose); (2) "El Crisantemo" (The Chrysanthemum); (3) "La Amapola" (The Poppy); (4) "Ojos de Dios" (God's Eyes); (5) "Ojitos con dos caras" (Two-Sided…
Instructional Resources. The Significance of Form: Ceramics.

ERIC Educational Resources Information Center

Zawatsky, Carole; And Others

1989-01-01

Presents four lesson plans designed to teach K-12 students about ceramics and the artists using the medium. Each lesson is centered around one ceramic piece: (1) "Wall Clock," by the Chantilly Porcelain Factory; (2) "Poppy Vase," by Adelaide Robineau; (3) "Laughing Eyes," by Pablo Picasso; and (4) "Ceramic Drum Jar," by Tsayutitsa. (GEA)
Application of membrane and ozonation technologies to remove color from agro-industry effluents.

PubMed

Koyuncu, I; Sevimli, M F; Ozturk, I; Aydin, A F

2001-01-01

The results of membrane and ozonation experiments carried out on various agro-industry effluents including fermentation (baker's yeast), corrugated board, opium alkaloid and textile dying industries are presented. The experiments were performed using lab-scale membrane and ozonation reactors. Color removals were in the range of 80 to 99% for the membrane treatment studies. Ozonation experiments have shown that color removals in the range of 83 to 98% are possible for the investigated wastewaters. Final color levels were lower than 100 Pt-Co unit, which is quite acceptable aesthetically. The relative unit treatment costs of ozonation were about two times higher than membrane systems especially for very strong colored effluents including fermentation and opium alkaloid industries. The study has demonstrated that both membrane and ozonation technologies are viable options for color removal.
Conservation and canalization of gene expression during angiosperm diversification accompany the origin and evolution of the flower

PubMed Central

Chanderbali, André S.; Yoo, Mi-Jeong; Zahn, Laura M.; Brockington, Samuel F.; Wall, P. Kerr; Gitzendanner, Matthew A.; Albert, Victor A.; Leebens-Mack, James; Altman, Naomi S.; Ma, Hong; dePamphilis, Claude W.; Soltis, Douglas E.; Soltis, Pamela S.

2010-01-01

The origin and rapid diversification of the angiosperms (Darwin's “Abominable Mystery”) has engaged generations of researchers. Here, we examine the floral genetic programs of phylogenetically pivotal angiosperms (water lily, avocado, California poppy, and Arabidopsis) and a nonflowering seed plant (a cycad) to obtain insight into the origin and subsequent evolution of the flower. Transcriptional cascades with broadly overlapping spatial domains, resembling the hypothesized ancestral gymnosperm program, are deployed across morphologically intergrading organs in water lily and avocado flowers. In contrast, spatially discrete transcriptional programs in distinct floral organs characterize the more recently derived angiosperm lineages represented by California poppy and Arabidopsis. Deep evolutionary conservation in the genetic programs of putatively homologous floral organs traces to those operating in gymnosperm reproductive cones. Female gymnosperm cones and angiosperm carpels share conserved genetic features, which may be associated with the ovule developmental program common to both organs. However, male gymnosperm cones share genetic features with both perianth (sterile attractive and protective) organs and stamens, supporting the evolutionary origin of the floral perianth from the male genetic program of seed plants. PMID:21149731
Conservation and canalization of gene expression during angiosperm diversification accompany the origin and evolution of the flower.

PubMed

Chanderbali, André S; Yoo, Mi-Jeong; Zahn, Laura M; Brockington, Samuel F; Wall, P Kerr; Gitzendanner, Matthew A; Albert, Victor A; Leebens-Mack, James; Altman, Naomi S; Ma, Hong; dePamphilis, Claude W; Soltis, Douglas E; Soltis, Pamela S

2010-12-28

The origin and rapid diversification of the angiosperms (Darwin's "Abominable Mystery") has engaged generations of researchers. Here, we examine the floral genetic programs of phylogenetically pivotal angiosperms (water lily, avocado, California poppy, and Arabidopsis) and a nonflowering seed plant (a cycad) to obtain insight into the origin and subsequent evolution of the flower. Transcriptional cascades with broadly overlapping spatial domains, resembling the hypothesized ancestral gymnosperm program, are deployed across morphologically intergrading organs in water lily and avocado flowers. In contrast, spatially discrete transcriptional programs in distinct floral organs characterize the more recently derived angiosperm lineages represented by California poppy and Arabidopsis. Deep evolutionary conservation in the genetic programs of putatively homologous floral organs traces to those operating in gymnosperm reproductive cones. Female gymnosperm cones and angiosperm carpels share conserved genetic features, which may be associated with the ovule developmental program common to both organs. However, male gymnosperm cones share genetic features with both perianth (sterile attractive and protective) organs and stamens, supporting the evolutionary origin of the floral perianth from the male genetic program of seed plants.
Selective boron delivery by intra-arterial injection of BSH-WOW emulsion in hepatic cancer model for neutron capture therapy

PubMed Central

Dewi, Novriana; Higashi, Syushi; Ikushima, Ichiro; Seguchi, Koji; Mizumachi, Ryoji; Murata, Yuji; Morishita, Yasuyuki; Shinohara, Atsuko; Mikado, Shoji; Yasuda, Nakahiro; Fujihara, Mitsuteru; Sakurai, Yuriko; Mouri, Kikue; Yanagawa, Masashi; Iizuka, Tomoya; Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shin-ichiro; Tanaka, Hiroki; Matsukawa, Takehisa; Yokoyama, Kazuhito; Fujino, Takashi; Ogura, Koichi; Nonaka, Yasumasa; Sugiyama, Hirotaka; Kajiyama, Tetsuya; Yui, Sho; Nishimura, Ryohei; Ono, Koji; Takamoto, Sinichi; Nakajima, Jun; Ono, Minoru; Eriguchi, Masazumi; Hasumi, Kenichiro; Takahashi, Hiroyuki

2017-01-01

Objective: Boron neutron-capture therapy (BNCT) has been used to inhibit the growth of various types of cancers. In this study, we developed a 10BSH-entrapped water-in-oil-in-water (WOW) emulsion, evaluated it as a selective boron carrier for the possible application of BNCT in hepatocellular carcinoma treatment. Methods: We prepared the 10BSH-entrapped WOW emulsion using double emulsification technique and then evaluated the delivery efficacy by performing biodistribution experiment on VX-2 rabbit hepatic tumour model with comparison to iodized poppy-seed oil mix conventional emulsion. Neutron irradiation was carried out at Kyoto University Research Reactor with an average thermal neutron fluence of 5 × 1012 n cm−2. Morphological and pathological analyses were performed on Day 14 after neutron irradiation. Results: Biodistribution results have revealed that 10B atoms delivery with WOW emulsion was superior compared with those using iodized poppy-seed oil conventional emulsion. There was no dissemination in abdomen or lung metastasis observed after neutron irradiation in the groups treated with 10BSH-entrapped WOW emulsion, whereas many tumour nodules were recognized in the liver, abdominal cavity, peritoneum and bilateral lobes of the lung in the non-injected group. Conclusion: Tumour growth suppression and cancer-cell-killing effect was observed from the morphological and pathological analyses of the 10BSH-entrapped WOW emulsion-injected group, indicating its feasibility to be applied as a novel intra-arterial boron carrier for BNCT. Advances in knowledge: The results of the current study have shown that entrapped 10BSH has the potential to increase the range of therapies available for hepatocellular carcinoma which is considered to be one of the most difficult tumours to cure. PMID:28406315
77 FR 16262 - Importer of Controlled Substances, Notice of Registration; Johnson Matthey, Inc., Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... substances: Drug Schedule Coca Leaves (9040) II Thebaine (9333) II Opium, raw (9600) II Noroxymorphone (9668... raw materials, to be used in the manufacture of bulk controlled substances, for distribution to its customers. In regard [[Page 16263

The heroin addict! A personal view.

PubMed

Cyngler, Charles

2002-04-01

Heroin beckons like the sweet seductive calls of Ulysses' sirens. The alluring nectar of the poppy seed, once experienced is not easy to escape. The greed for pleasure is endless. Gratification begets gratification. This paper explores issues and complications of treatment intervention in heroin addiction. The author is a general practitioner with 25 years experience and special interest in substance abuse medicine.
Drug Dependency: A Legacy from the Past.

ERIC Educational Resources Information Center

Labianca, Dominick A.; Reeves, William J.

1984-01-01

In the nineteenth century people consumed opium in the form of laudanum to relieve their anxieties. Today drug abuse has become a problem of epic proportions. For a segment of our society, chemicals represent relief from physical and mental pain. (CS)
Application of hydrostatic CCC-TLC-HPLC-ESI-TOF-MS for the bioguided fractionation of anticholinesterase alkaloids from Argemone mexicana L. roots.

PubMed

Kukula-Koch, Wirginia; Mroczek, Tomasz

2015-03-01

A rapid hydrostatic counter-current chromatography-thin-layer chromatography-electrospray-ionization time-of-flight mass spectrometry (CCC-TLC-ESI-TOF-MS) technique was established for use in seeking potent anti-Alzheimer's drugs among the acethylcholinesterase inhibitors in Argemone mexicana L. underground parts, with no need to isolate components in pure form. The dichloromethane extract from the roots of Mexican prickly poppy that was most rich in secondary metabolites was subjected to hydrostatic-CCC-based fractionation in descending mode, using a biphasic system composed of petroleum ether-ethyl acetate-methanol-water at the ratio of 1.5:3:2.1:2 (v/v). The obtained fractions were analyzed in a TLC-based AChE-inhibition "Fast Blue B" test. All active components in the fractions, including berberine, protopine, chelerithrine, sanguinarine, coptisine, palmatine, magnoflorine, and galanthamine, were identified in a direct TLC-HPLC-ESI-TOF-MS assay with high accuracy. This is the first time galanthamine has been reported in the extract of Mexican prickly poppy and the first time it has been identified in any member of the Papaveraceae family, in the significant quantity of 0.77%.
78 FR 64015 - Importer of Controlled Substances, Notice of Registration, Siegfried (USA), LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances, Notice of..., New Jersey 08070, made application by letter to the Drug Enforcement Administration (DEA) to be registered as an importer of the following basic classes of controlled substances: Drug Schedule Opium, raw...
Substance abuse among Iranian high school students.

PubMed

Momtazi, Saeed; Rawson, Richard

2010-05-01

In this study, we reviewed data on drug use among high school students in Iran. Published epidemiological studies in international and domestic journals show that drug use/abuse is a serious mental health problem in Iran. There is cultural support for opium in Iran and also there is cultural tolerance for tobacco smoking, especially as water pipe smoking in Iranian families. Alcohol, opium and cannabis are the most frequently used illicit drugs, but there are new emerging problems with anabolic steroids, ecstasy and stimulant substances, such as crystal methamphetamine. There is a serious drug abuse problem among Iranian high school students. It could be due to role modeling by parents - mainly fathers - and also cultural tolerance of some substances. Early onset of tobacco smoking, with a daily use rate between 4.4 and 12.8% in high school students, is an important risk factor for other drug abuse problems. Use of all types of drugs, except prescription drugs, is more prevalent among boys. Alcohol is the most frequently abused substance, with a lifetime rate of at least 9.9%. Lifetime rates of opiate use - mostly opium - was between 1.2 and 8.6% in different parts of the country. As drug abuse is a frequent problem among Iranian high school students, it is necessary to design and implement drug prevention programs to protect them. Such programs, including life skills training and drug education, have been operating in recent years for Iranian students from kindergarten to the university level.
Profile of People Who Inject Drugs in Tehran, Iran.

PubMed

Amin-Esmaeili, Masoumeh; Rahimi-Movaghar, Afarin; Gholamrezaei, Maryam; Razaghi, Emran Mohammad

2016-12-01

The marked shift in the patterns of drug use in Iran, from opium smoking to injecting drug use, has led to serious health-related outcomes. This study was designed to explore characteristics of people who inject drugs (PWID) in Tehran, Iran. Nine hundred and four PWID were recruited from treatment and harm reduction facilities, as well as drug user hangouts in public areas in Tehran. Participants were interviewed using the Persian version of the World Health Organization Drug Injecting Study Phase II questionnaire. The median age at the time of the first illegal drug use, at the time of the first injection and current age was 20, 24 and 32, respectively. In more than 80% of the cases, the first drug used was opium. The transition from the first drug use to the first drug injection occurred after an average of 6.6 and 2.7 years for those who had started drug use with opium and heroin, respectively. Two-thirds of the participants shared injecting equipment within the last 6 months. Difficulty in obtaining sterile needles and thehigh cost of syringes were reported as the major reasons for needle/syringe sharing. Approximately 80% of community-recruited PWID reported difficulties in using treatment or harm reduction services. Self-detoxification and forced detoxification were the most common types of drug abuse treatment in alifetime. Despite a dramatic shift in drug policy in Iran during the past few years, wider coverage of harm reduction services, improvement of the quality of services, and education about such services are still necessary.
Substance Abuse among Iranian High School Students

PubMed Central

Momtazi, Saeed; Rawson, Richard A.

2015-01-01

Purpose of review In this study, we reviewed data on drug use among high school students in Iran. Recent findings Published epidemiological studies in international and domestic journals show that drug use/abuse is a serious mental health problem in Iran. There is cultural support for opium in Iran, and also there is cultural tolerance for tobacco smoking, especially as water pipe smoking, in Iranian families. Alcohol, opium, and cannabis are the most frequently used illicit drugs, but there are new emerging problems with anabolic steroids, ecstasy, and stimulant substances, such as crystal methamphetamine. Summary There is serious drug abuse problem among Iranian high school students. It could be due to role-modeling by parents – mainly fathers – and also cultural tolerance of some substances. Early onset of tobacco smoking, with a daily use rate between 4.4% and 12.8% in high school students, is an important risk factor for other drug abuse problems. Use of all types of drugs, except prescription drugs, is more prevalent among boys. Alcohol is the most frequently abused substance, with a lifetime rate of at least 9.9%. Lifetime rates of opiate use – mostly opium – were between 1.2 an 8.6% in different parts of the country. As drug abuse is a frequent problem among Iranian high school students, it is necessary to design and implement drug prevention programs to protect them. Such programs, including life skills training and drug education, have been operating in recent years for Iranian students from kindergarten to the university level. PMID:20308905
Translations on Narcotics and Dangerous Drugs, Number 310

DTIC Science & Technology

1977-07-14

for burning by the justice department under the supervision of the medicine control service. 6244 CSO: 5300 42 BRAZIL SEIZURE OF MARIHUANA ...Seized in Prome 13 Destruction of Poppies, Marihuana 13 Heroin Seized 13 Police Seize More Heroin 14 JAPAN Police Arrest Three for Smuggling Drugs...Trafficker Sentenced 29 THAILAND Police Arrest 17 on Marihuana Smuggling Charges (MORNING EXPRESS, 5 Jul 77) 30 Briefs Drug Rings Suspend
Property & Peace: Insurgency, Strategy and the Statute of Frauds

DTIC Science & Technology

2009-05-01

Colombia: Fragmented 125 quinine, ink, feathers, fur, flowers , gold, oil, poppy, sugar, cattle – all these saleable items and many others have...easily includes ink, leather, edible rodents, hardwoods, African palm oil, cigarettes, quinine, counterfeit monies, music CDs, bananas , etc. The smuggling...lesser resources spurring armed violence, not the least of which are bananas , coffee and African palm.122 Admitting many commonalities, each of these
Wildlife for sale.

PubMed

Martin, E; Redford, T

2000-02-01

Myanmar, famous for the smuggling of opium and gemstones, is losing much of its wildlife to illegal traders. In 1998, a survey of goods for sale in two border towns showed a thriving trade in body parts from some of the world's most endangered species.
78 FR 64021 - Manufacturer of Controlled Substances; Notice of Registration; Noramco, Inc. (GA)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances... application to the Drug Enforcement Administration (DEA) to be registered as a bulk manufacturer of Opium... laws, and a review of the company's background and history. Therefore, pursuant to 21 U.S.C. 823(a...
3 CFR - Presidential Determination on Major Illicit Drug Transit or Major Illicit Drug Producing...

Code of Federal Regulations, 2010 CFR

2010-01-01

... between opium production, the resulting narcotics trade, corruption, and the insurgency continues to grow... the Swat Valley. The Government of Pakistan was compelled to divert manpower and equipment resources... 2008 resulted in the seizure of 21.7 and 19.5 metric tons of cocaine seizures, respectively. The...
Plants and Medicinal Chemistry

ERIC Educational Resources Information Center

Bailey, D.

1977-01-01

This is the first of two articles showing how plants that have been used in folk medicine for many centuries are guiding scientists in the design and preparation of new and potent drugs. Opium and its chemical derivatives are examined at length in this article. (Author/MA)
Hong Kong Junk: Plague and the Economy of Chinese Things.

PubMed

Peckham, Robert

2016-01-01

Histories of the Third Plague Pandemic, which diffused globally from China in the 1890s, have tended to focus on colonial efforts to regulate the movement of infected populations, on the state's draconian public health measures, and on the development of novel bacteriological theories of disease causation. In contrast, this article focuses on the plague epidemic in Hong Kong and examines colonial preoccupations with Chinese "things" as sources of likely contagion. In the 1890s, laboratory science invested plague with a new identity as an object to be collected, cultivated, and depicted in journals. At the same time, in the increasingly vociferous anti-opium discourse, opium was conceived as a contagious Chinese commodity: a plague. The article argues that rethinking responses to the plague through the history of material culture can further our understanding of the political consequences of disease's entanglement with economic and racial categories, while demonstrating the extent to which colonial agents "thought through things."
Heroin overdose deaths and heroin purity between 1990 and 2000 in Istanbul, Turkey*.

PubMed

Toprak, Sadik; Cetin, Ilhan

2009-09-01

Turkey has continuously experienced problems with abuse of, and addiction to, opium derivatives. In this study, we analyzed the relationship between heroin overdose deaths and the characteristics of seized opium derivatives. Data were gathered from the Council of Forensic Medicine of the Ministry of Justice in Istanbul from 1990 to 2000. There were 636 heroin-related deaths during this period, 595 of which were classified as heroin overdose deaths. Mean crude and weighted heroin purities remained relatively constant and were calculated to be 46% (57-34%) and 51% (39-59%), respectively. The weight of heroin and the number of heroin seizures, but not the heroin purity, were significantly associated with the number of heroin-related deaths. Prevention strategies are needed to reduce the number of deaths caused by overdoses in countries situated on drug trafficking routes. These strategies should focus on drug trafficking, by providing increased levels of, and support for, law enforcement, stopping the supply of precursor chemicals, and combating corruption among border officials.
AU-18 Space Primer

DTIC Science & Technology

2009-09-01

force air and space component commander (CFACC) should be des - ignated as the supported commander for counterspace operations. • To plan , execute, and...performing COMINT and/or FISINT activities. Figure 13-10. Poppy satellite with multiface de - sign. (Photo taken by the NRL and provided cour- tesy of the...SATCOM) Planning Information Network SPO special projects office; system programs office SPOT Satellite Pour L’Observation de la Terre SPS
Second generation benzofuranone ring substituted noscapine analogs: Synthesis and biological evaluation

PubMed Central

Mishra, Ram Chandra; Karna, Prasanthi; Gundala, Sushma Reddy; Pannu, Vaishali; Stanton, Richard A.; Gupta, Kamlesh Kumar; Robinson, Mary; Lopus, Manu; Wilson, Leslie; Henary, Maged; Aneja, Ritu

2011-01-01

Microtubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems. Noscapinoids represent an emerging class of microtubule-modulating anticancer agents based upon the parent molecule noscapine, a naturally-occurring non-toxic cough-suppressant opium alkaloid. Here we report in silico molecular modeling, chemical synthesis and biological evaluation of novel analogs derived by modification at position-7 of the benzofuranone ring system of noscapine. The synthesized analogs were evaluated for their tubulin polymerization activity and their biological activity was examined by their antiproliferative potential using representative cancer cell lines from varying tissue-origin [A549 (lung), CEM (lymphoma), MIA PaCa-2 (pancreatic), MCF-7 (breast) and PC-3 (prostate)]. Cell-cycle studies were performed to explore their ability to halt the cell-cycle and induce subsequent apoptosis. The varying biological activity of these analogs that differ in the nature and bulk of substituent at position-7 was rationalized utilizing predictive in silico molecular modeling. PMID:21501599
Students and Drugs at NCSU: 1977-1978 Report.

ERIC Educational Resources Information Center

Fuller, Earl H.

A survey conducted in 1977 at North Carolina State University on drugs was designed to measure usage rates for four types of drugs: marijuana, hallucinogens (such as LSD, mescaline, and psilocybin); amphetamines and barbituates; and narcotics (heroin, opium, and morphine). The questionnaire was also designed to determine student attitudes on…
Translations on Narcotics and Dangerous Drugs, Number 299

DTIC Science & Technology

1977-05-11

A six-man party led by the deputy OCPD [Officer in Charge of Police Department], acting ASP [Assistant Superintendent of Police] Tang Yau Hie also...just prepared from opium when police moved in. The stoves were still burning and some drugs were recovered from the pans. Kulim OCPD Deputy Supt
Report on Progress Toward Security and Stability in Afghanistan and United States Plan for Sustaining the Afghanistan National Security Forces

DTIC Science & Technology

2011-04-01

Ug99 stem rust resistant wheat breeder seed to MAIL, which will be released to farmers for commercial planting in fall 2011. Poppy yields decreased...level continues to improve the Afghan Government’s overall agricultural sector. Wheat is a key staple in Afghanistan, accounting for over one-half of...tight global supply could affect the country’s food security. Afghanistan’s wheat production routinely does not meet demand and is subject to sizable

A Resource Network Strategy for Afghanistan

DTIC Science & Technology

2013-12-01

collectors and investment purposes. Additionally, gold is used in treating a small number of medical conditions such as rheumatoid arthritis and cancer ...such as medical care. Mullahs are often chosen and known for their piety, wisdom, formal and/or informal education in Islamic tradition and Muslim laws...exports in 2012 was modestly estimated at $2 billion while the net export value of opiates was $1.94 billion. Cannabis is closely related to poppy
Drug Abuse. A Guide for Parents and Teachers.

ERIC Educational Resources Information Center

St. Souver, F. Gerald; Plunkett, Thomas G.

This booklet is concerned with providing information on drug abuse. A brief history of drug traffic and today's problem begin the pamphlet. The second part discusses the identification of drugs including opium, heroin, and marihuana. The next section is concerned with non-narcotic drug abuse, including Lysergic Acid Diethylamide (LSD) mascaline,…
Multimorbidity: Epidemiology and Risk Factors in the Golestan Cohort Study, Iran

PubMed Central

Ahmadi, Batoul; Alimohammadian, Masoomeh; Yaseri, Mehdi; Majidi, Azam; Boreiri, Majid; Islami, Farhad; Poustchi, Hossein; Derakhshan, Mohammad H.; Feizesani, Akabar; Pourshams, Akram; Abnet, Christian C.; Brennan, Paul; Dawsey, Sanford M.; Kamangar, Farin; Boffetta, Paolo; Sadjadi, Alireza; Malekzadeh, Reza

2016-01-01

Abstract Advances in medicine and health policy have resulted in growing of older population, with a concurrent rise in multimorbidity, particularly in Iran, as a country transitioning to a western lifestyle, and in which the percent of the population over the age of 60 years is increasing. This study aims to assess multimorbidity and the associated risk factors in Iran. We used data from 50,045 participants (age 40–75 y) in the Golestan Cohort Study, including data on demographics, lifestyle habits, socioeconomic status, and anthropometric indices. Multimorbidity was defined as the presence of 2 or more out of 8 self-reported chronic conditions, including cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, gastroesophageal reflux disease, tuberculosis, and cancer. Multivariate logistic regression models were used to examine the associations between multiple different factors and the risk factors. Multimorbidity prevalence was 19.4%, with the most common chronic diseases being gastroesophageal reflux disease (76.7%), cardiovascular diseases (72.7%), diabetes (25.3%), and chronic obstructive pulmonary disease (21.9%). The odds of multimorbidity was 2.56-fold higher at the age of >60 years compared with that at <50 years (P < 0.001), and 2.11-fold higher in women than in men (P < 0.001). Other factors associated with higher risk of multimorbidity included non-Turkmen ethnicity, low education, unemployment, low socioeconomic status, physical inactivity, overweight, obesity, former smoking, opium and alcohol use, and poor oral health. Apart from advanced age and female sex, the most important potentially modifiable lifestyle factors, including excess body weight and opium use, and opium user, are associated with multimorbidity. Policies aiming at controlling multimorbidity will require a multidimensional approach to reduce modifiable risk factors in the younger population in developing countries
Contribution of Ruminal Fungi, Archaea, Protozoa, and Bacteria to the Methane Suppression Caused by Oilseed Supplemented Diets

PubMed Central

Wang, Shaopu; Giller, Katrin; Kreuzer, Michael; Ulbrich, Susanne E.; Braun, Ueli; Schwarm, Angela

2017-01-01

Dietary lipids can suppress methane emission from ruminants, but effects are variable. Especially the role of bacteria, archaea, fungi and protozoa in mediating the lipid effects is unclear. In the present in vitro study, archaea, fungi and protozoa were selectively inhibited by specific agents. This was fully or almost fully successful for fungi and protozoa as well as archaeal activity as determined by the methyl-coenzyme M reductase alpha subunit gene. Five different microbial treatments were generated: rumen fluid being intact (I), without archaea (–A), without fungi (–F), without protozoa (–P) and with bacteria only (–AFP). A forage-concentrate diet given alone or supplemented with crushed full-fat oilseeds of either safflower (Carthamus tinctorius) or poppy (Papaver somniferum) or camelina (Camelina sativa) at 70 g oil kg−1 diet dry matter was incubated. This added up to 20 treatments with six incubation runs per treatment. All oilseeds suppressed methane emission compared to the non-supplemented control. Compared to the non-supplemented control, –F decreased organic matter (OM) degradation, and short-chain fatty acid concentration was greater with camelina and safflower seeds. Methane suppression per OM digested in –F was greater with camelina seeds (−12 vs.−7% with I, P = 0.06), but smaller with poppy seeds (−4 vs. −8% with I, P = 0.03), and not affected with safflower seeds. With –P, camelina seeds decreased the acetate-to-propionate ratio and enhanced the methane suppression per gram dry matter (18 vs. 10% with I, P = 0.08). Hydrogen recovery was improved with –P in any oilseeds compared to non-supplemented control. No methane emission was detected with the –A and –AFP treatments. In conclusion, concerning methanogenesis, camelina seeds seem to exert effects only on archaea and bacteria. By contrast, with safflower and poppy seeds methane was obviously reduced mainly through the interaction with protozoa or archaea associated
Contribution of Ruminal Fungi, Archaea, Protozoa, and Bacteria to the Methane Suppression Caused by Oilseed Supplemented Diets.

PubMed

Wang, Shaopu; Giller, Katrin; Kreuzer, Michael; Ulbrich, Susanne E; Braun, Ueli; Schwarm, Angela

2017-01-01

Dietary lipids can suppress methane emission from ruminants, but effects are variable. Especially the role of bacteria, archaea, fungi and protozoa in mediating the lipid effects is unclear. In the present in vitro study, archaea, fungi and protozoa were selectively inhibited by specific agents. This was fully or almost fully successful for fungi and protozoa as well as archaeal activity as determined by the methyl-coenzyme M reductase alpha subunit gene. Five different microbial treatments were generated: rumen fluid being intact (I), without archaea (-A), without fungi (-F), without protozoa (-P) and with bacteria only (-AFP). A forage-concentrate diet given alone or supplemented with crushed full-fat oilseeds of either safflower ( Carthamus tinctorius ) or poppy ( Papaver somniferum ) or camelina ( Camelina sativa ) at 70 g oil kg -1 diet dry matter was incubated. This added up to 20 treatments with six incubation runs per treatment. All oilseeds suppressed methane emission compared to the non-supplemented control. Compared to the non-supplemented control, -F decreased organic matter (OM) degradation, and short-chain fatty acid concentration was greater with camelina and safflower seeds. Methane suppression per OM digested in -F was greater with camelina seeds (-12 vs.-7% with I, P = 0.06), but smaller with poppy seeds (-4 vs. -8% with I, P = 0.03), and not affected with safflower seeds. With -P, camelina seeds decreased the acetate-to-propionate ratio and enhanced the methane suppression per gram dry matter (18 vs. 10% with I, P = 0.08). Hydrogen recovery was improved with -P in any oilseeds compared to non-supplemented control. No methane emission was detected with the -A and -AFP treatments. In conclusion, concerning methanogenesis, camelina seeds seem to exert effects only on archaea and bacteria. By contrast, with safflower and poppy seeds methane was obviously reduced mainly through the interaction with protozoa or archaea associated with protozoa. This
25 CFR 140.19 - Drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Drugs. 140.19 Section 140.19 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LICENSED INDIAN TRADERS § 140.19 Drugs. Traders shall not keep for sale, or sell, give away, or use any opium, chloral, cocaine, peyote or mescal bean...
25 CFR 140.19 - Drugs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Drugs. 140.19 Section 140.19 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LICENSED INDIAN TRADERS § 140.19 Drugs. Traders shall not keep for sale, or sell, give away, or use any opium, chloral, cocaine, peyote or mescal bean...
25 CFR 140.19 - Drugs.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Drugs. 140.19 Section 140.19 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LICENSED INDIAN TRADERS § 140.19 Drugs. Traders shall not keep for sale, or sell, give away, or use any opium, chloral, cocaine, peyote or mescal bean...
25 CFR 140.19 - Drugs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Drugs. 140.19 Section 140.19 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LICENSED INDIAN TRADERS § 140.19 Drugs. Traders shall not keep for sale, or sell, give away, or use any opium, chloral, cocaine, peyote or mescal bean...
25 CFR 140.19 - Drugs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Drugs. 140.19 Section 140.19 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LICENSED INDIAN TRADERS § 140.19 Drugs. Traders shall not keep for sale, or sell, give away, or use any opium, chloral, cocaine, peyote or mescal bean...
Early Twentieth Century Responses to the Drug Problem.

ERIC Educational Resources Information Center

Pfennig, Dennis Joseph

1991-01-01

Describes early twentieth-century responses to the drug problem in the United States. Discusses pressure from the media and reformers to control the availability of drugs such as opium and cocaine that were widely available in over-the-counter medications. Focuses on New York State, which took the lead in enacting drug control legislation. (DK)
Political Economy of Drugs and Insurgency: The Case of Punjab

DTIC Science & Technology

2017-03-01

in tourism, and agriculture when drugs such as poppy and marijuana are chosen for their profits over cultivating food needed for the nation.53 Punjab...on agriculture ” as the key reasons for Punjab’s economic slowdown.59 Of these factors, poor governance falls right into the hands of those actors...71 It is a fertile region with a large amount of land devoted to agriculture . India’s 2011 census estimated Punjab’s population to be 27.7 million
The Rise of Women's Modern Schooling in Late Qing China (1840-1911)

ERIC Educational Resources Information Center

Liu, Xiaoyi

2009-01-01

The rise of women's modern schooling in late Qing China was deemed to be, by the historical trend of modern China, a progress that coincided with China's modernization and national self-strengthening movement after the humiliating defeat of the Opium War. This article is an examination of this process from 1840 to 1911, which had undergone three…
A Brief History of American Drug Control.

ERIC Educational Resources Information Center

Musto, David F.

1991-01-01

Traces the history of drug control in the United States from the extensive consumption of opium, heroin, and cocaine before World War I to the popularity of marijuana and LSD during the 1960s. Discusses public concern over drug use that seems to peak following periods of widespread drug use that is linked to foreign influences. (DK)
[The War on "Red Drugs": Anticommunism and Drug Policy in Republic of Korea, 1945-1960].

PubMed

Park, Ji-Young

2016-04-01

This paper investigates the discourses and policies on narcotics in Republic of Korea from 1945 to 1960. Since the Liberation the narcotic problem was regarded as the vestige of Japanese imperialism. which was expected to be cleaned up. The image of narcotic crimes as the legacy of the colonial past was turned into as the result of the Red Army's tactics to attack on the liberalist camp around the Korean war. The government of ROK represented the source of the illegal drugs as the Red army and the spy from North Korea. The anticommunist discourse about narcotics described the spies, who introduced the enormous amount of poppies into ROK and brought about the addicts, as the social evil. Through this discourse on poppies from North Korea, the government of ROK emphasized the immorality of the communists reinforcing the anticommunist regime, which was inevitable for the government of ROK to legitimize the division of Korea and the establishment of the government alone. This paper examines how the discourses and policies on narcotics in ROK was shaped and transformed from 1945 to 1960 focusing the relationship between the them and the political context such as anticommunism, Korean war, the division of Korea, and etc. This approach would be helpful to reveal the effect of the ROK's own political situation to the public health system involving the management for drugs.
Translations on Narcotics and Dangerous Drugs, Number 277

DTIC Science & Technology

1976-12-23

17 Nov 76) 17 MEXICO U. S. Demand Fosters Sinaloa Drug Production (EXCELSIOR, l6 Nov 76) 18 American Never Set Foot in Prison (EL DIARIO DE ...NUEVO LAREDO, 28 Oct 76) 20 Weapons, Poppies and Marihuana Fall to Army Campaign (EL SOL DE MEXICO, l6 Nov 76) 21 Charge No Action Taken...Against Drugs (EL DIARIO, 25 Oct 76) 22 Rafael Chavez Baldazo Arrested (EL DIARIO, 1 Nov 76) 23 ’Don Cuco’ Gang Smashed (DIARIO DE NOGALES
To Legalize or not to Legalize? That is the Question

DTIC Science & Technology

2009-04-01

and international community to improve security and promote development in Afghanistan. The negative effect on the nations overall security, the...the problem/solution methodology. The research explores the current illicit opium cultivation in Afghanistan and its effect on the current...negative effect on the current development efforts. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF
Poppy Eradication in Afghanistan: Why Isn’t It Working?

DTIC Science & Technology

2009-03-17

convulsions, fever • Complications from intravenous use: infections from contaminated needles, hepatitis, TB, tetanus, pneumonia, bacterial... endocarditis NOTE: The Controlled Substances Act is part ofTitle II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The purpose is to
Acceptability of the Current and Proposed Items in the Meal, Ready-to-Eat

DTIC Science & Technology

2002-05-01

Cayenne pepper and Mrs. Dash), and dessert items (Peanut Butter M&Ms, Crispy M&Ms, Pumpkin Pound cake, Almond Poppy Pound cake, and a Chocolate Mint...Almost Every Entree 16.34 Every Entree 22.18 Because the Cayenne pepper and Mrs. Dash are not included in the current MREs, the soldiers were asked... pepper . Half(54.47%) wish to have Hot sauce in ’·every/almost every’· entree (Table 3). Forty percent (43.29%) would like to have Cayenne pepper "never
Potential dangers of cannabis.

PubMed

Kaymakçalan, S

1975-01-01

Cannabis is not a harmless drug. The potential dangers of cannabis are briefly reviewed in this report. The above-mentioned observations on cannabis users should be kept in mind and carefully examined by all physicians. One could expect that as more potent cannabis preparations become available, some of the toxic manifestations which now seem rare might become more frequent. Some of the remarks about the dangers of cannabis may not be proved in future studies, and they may represent only our anxiety. However, prior to the elimination of these fears, no steps should be taken toward the legalizing of marijuana. At present there is no scientific evidence that cannabis is less harmful than either tobacco or alcohol. The opposite may be true. The analogy can be drawn between opium and cannabis. The permissive attitude toward the use of opium can easily lead to the use of morphine and other opiates. If we legalize the use of marijuana, we cannot prevent the use of more dangerous derivatives of cannabis; namely, hashish, cannabis oil and THC, itself. In my opinion, in the light of our present knowledge, legalizing of marijuana could be hazardous both for the individual and for society.

Agriculture Development in Afghanistan: A Systemic Assessment Approach

DTIC Science & Technology

2010-04-14

Sponsoring programs to improve the health orpeople, livestock, and crops. 5. Distributing high-quality seeds and fertilizers.3 The USDA lists close to...weapons, and smuggling. The Taliban joined warlords and both entities offer credit, seeds , and fertilizer to farmers who grow and cultivated opium. The... seed , fertilizer, pesticide, storage, processing, and packaging; however, a review of the most challenging inputs validate the proposed assessment
Translations on Narcotics and Dangerous Drugs, Number 280.

DTIC Science & Technology

1977-01-13

ESPECTADOR, 29 Nov 76) 28 Briefs Cocaine, Weapons Seizure 29 Marihuana Traffickers 29 Foreign Traffickers Deported 29 Colombian Drug Trafficker 30...learned that a U Tha U-led suppression squad is endeavoring to take decisive action against heroin, opium, and marihuana users and pethidine...though our government also considers amphetamines as banned drugs, since their raw materials have other uses in medicine , their trade is not
Drug Trafficking and North Korea: Issues for U.S. Policy

DTIC Science & Technology

2006-11-27

profoundly troubling.... [T]he United States has not been able to determine the extent to which the North Korean Government is involved in manufacturing and...indications especially from the series of methamphetamine seizures in Japan that North Koreans traffic in and probably manufacture methamphetamine...refines opium into heroin, and manufactures methamphetamine drugs in North Korea as a state-organized and directed activity, with the objective of
Visible-light driven nitrogen-doped petal-morphological ceria nanosheets for water splitting

NASA Astrophysics Data System (ADS)

Qian, Junchao; Zhang, Wenya; Wang, Yaping; Chen, Zhigang; Chen, Feng; Liu, Chengbao; Lu, Xiaowang; Li, Ping; Wang, Kaiyuan; Chen, Ailian

2018-06-01

Water splitting is a promising sustainable technology for solar-to-chemical energy conversion. Herein, we successfully fabricated nitrogen-doped ultrathin CeO2 nanosheets by using field poppy petals as templates, which exhibit an efficiently catalytic activity for water splitting. Abundant oxygen vacancies and substitutional N atoms were experimentally observed in the film due to its unique biomorphic texture. In view of high efficiency and long durability of the as-prepared photocatalyst, this biotemplate method may provide an alternative technique for using biomolecules to assemble 2D nanomaterials.
Granular convection observed by magnetic resonance imaging.

PubMed

Ehrichs, E E; Jaeger, H M; Karczmar, G S; Knight, J B; Kuperman, V Y; Nagel, S R

1995-03-17

Vibrations in a granular material can spontaneously produce convection rolls reminiscent of those seen in fluids. Magnetic resonance imaging provides a sensitive and noninvasive probe for the detection of these convection currents, which have otherwise been difficult to observe. A magnetic resonance imaging study of convection in a column of poppy seeds yielded data about the detailed shape of the convection rolls and the depth dependence of the convection velocity. The velocity was found to decrease exponentially with depth; a simple model for this behavior is presented here.
Agriculture and stability in Afghanistan

DTIC Science & Technology

2009-05-21

national wealth are due to good political institutions. 16 He believes that geographical factors, including disproportionate disease burdens on human... Celia W. Dugger, “Ending Famine, Simply by Ignoring the Experts,” New York Times, December 2, 2007. 87 Dugger, Ending Famine, p 1. 88 J. Brian Atwood...is multidimensional, as well as a symptom of insecurity, corruption and poor governance. The Islamic Government of Afghanistan describes the opium
The Pashtun Behavior Economy: An Analysis of Decision Making in Tribal Society

DTIC Science & Technology

2011-06-01

SUB-SAHARAN AFRICA ) from the NAVAL POSTGRADUATE SCHOOL June 2011 Author: Jeremy W. Holton Approved by: Thomas H. Johnson...push up the market values of their own opium production farms .6 A. MAJOR RESEARCH QUESTION The anecdotes above reflect some of the most basic...Yet another proof has been given of the wave of fanaticism which is sweeping along the North -West frontier of India. Malakand was the scene last
Sherlock Holmes and anaesthesia.

PubMed

Maltby, J R

1988-01-01

Sir Arthur Conan Doyle's first Sherlock Holmes adventure, A Study in Scarlet, was published 100 years ago. Between 1887 and 1927 he wrote 56 short stories and four novels about his fictional detective. Episodes in the adventures which relate to anaesthetic drugs are described. Use of the drugs was criminal in the case of chloroform, opium, and curare; therapeutic in the case of morphine; and recreational when Holmes himself used cocaine.
U. S. Strategy for the Far East: Toward the 21st Century

DTIC Science & Technology

1989-03-31

countries: Indonesia, Malaysia , Thailand, Singapore, the Solomon Islands, Vanuatu, Tonga, Western Samoa, and Kiribati.10 The departure of New Zealand...American demands, a few South Korean firms have opened plants in America: Samsung manufactures TV’s in New Jersey. Another sensitive trade topic is...Pakistan, Malaysia , Hong Kong and India cooperate with the U.S. in our drug war efforts. Burma is the largest producer of opium, but recent domestic
Drug Violence Along the Southwest Border: Another American Punitive Expedition?

DTIC Science & Technology

2011-03-16

compelled some workers to cultivate marijuana and opium. As legal restrictions in the U.S. appeared in the 1960s, cartels began to facilitate the...violence is the recent involvement of paramilitary organizations within organized crime and the drug cartels in Mexico. Many of these organizations are...this increase in violence is the recent involvement of paramilitary organizations within organized crime and the drug cartels in Mexico. Many of
A Go-to-Market Strategy: Promoting Private Sector Solutions to the Threat of Proliferation

DTIC Science & Technology

2013-04-01

indicators reveal that these problems, often subsumed under the seemingly innocuous heading of “transnational threats,” are a growing cancer on the...trade is worth an estimated $322 billion annually with 52,356 metric tons of opium, cannabis , cocaine, and amphetamine-type stimulant (ATS...of medical isotopes to the sites that secure the material. 30 Regulators are also now starting to consider another critical component in the
International Drug Control Policy

DTIC Science & Technology

2008-06-23

domestic law or international drug control agreements. Narcotic drugs include cannabis, cannabis resin, coca leaf , cocaine, heroin, and opium...differently, a kilogram of powder cocaine is far more difficult to detect than the 300 to 500 kilograms of coca leaf that are required to make that same...1961 Convention gave countries practicing coca leaf chewing 25 years following the Convention’s entry into force to abolish coca leaf chewing. 85 See
International Drug Control Policy

DTIC Science & Technology

2009-02-09

control agreements.1 Narcotic drugs include cannabis, cannabis resin, coca leaf , cocaine, heroin, and opium. Psychotropic substances include ecstasy,2...cocaine is far more difficult to detect than the 300 to 500 kilograms of coca leaf that are required to make that same kilogram. Also, because crops...for legalizing the production and sale of coca leaf , which is currently an internationally controlled narcotic substance? And how can the United
Translations on Narcotics and Dangerous Drugs No. 286.

DTIC Science & Technology

1977-02-24

Source of Opium (Kyaw Min; THE WORKING PEOPLE’S DAILY, various dates) .. 46 MALAYSIA Antidrug Panels in Government Units To Be Set Up...Seized at Border 157 International Drug Ring Captured 157 Heroin Seized in Madrid 157 UNITED KINGDOM New Trial Ordered on Drugs Loophole Case (THE...are now only about eight months old, include: A big quantity of hashish contained in a welded, enclosed metal case ; Fourteen marihuana seeds
Navigating the Road to Reintegration: Status and Continuing Support of the U.S. Air Force’s Wounded Warriors

DTIC Science & Technology

2015-01-01

favorably to other response rates (see, e.g., Baruch, 1999, who reported declines in average response rates over the years such that the average in 1995 was...whether they had used marijuana ; other illicit drugs such as cocaine, opium, amphetamines, or Ecstasy (MDMA, or 3,4-methylenedioxy-N...reported use of marijuana or prescription medication other than as prescribed. The reported rates of marijuana use, again, are slightly higher than age
The Effects of NiTi Hand and Rotary Canal Master U and K-Flex Instrumentation of Root Canal Morphology

DTIC Science & Technology

1992-09-01

MOI•MMIfGY by Robert H. Haller Doctor of Dental Surgery 1983 University of Marjland School of Dentistry A research proposal submitted to the faculty...of the Endodontic Department of the JTiH.SCSA Dental Schcol in partial fulfillment of the requirements for a CERTIFICATE IN M[XfTICS Univxriity :)0...cauterizing the gulp with a hot instrument. In addition to hot instruments, many dental practitioners used boiling oil, herbs, opium, and arsenic to desiccate
To Determine if a Combined U.S. and Afghanistan Military-Civilian Counter-Narcotics Joint Task Force Should Be Created to Support the Fight Against Counterinsurgencies in the Afghan Theater of War

DTIC Science & Technology

2011-06-10

AFGHAN THEATER OF WAR, by Major Keith W. Alfeiri, 88 pages. The opium trade is a major funding source for the insurgency in Afghanistan. The Afghan...joint task force should be created to support the fight against counterinsurgencies in the Afghan theater of war. The drug trade has often been used to...remains that drugs fund terrorism and insurgents as the money flows between the drug trade and insurgents. According to a United Nations (UN
Translations on Narcotics and Dangerous Drugs, Number 288

DTIC Science & Technology

1977-03-10

benefits, U.S. medical researchers have found, and can be used to relieve the symptoms of glaucoma and asthma and as a tonic for terminal cancer ...DAILY TELEGRAPH, 11 Feb 77) 157 h - CONTENTS (Continued) Page Court Rules Possession of Cannabis Seed Not Illegal (Terence Shaw; THE DAILY...raw opium, or 200 grams of cannabis or cannabis resin or more, otherwise than in accordance with the authority of the ordinance or any other
Translations on Narcotics and Dangerous Drugs. Number 297

DTIC Science & Technology

1977-05-03

investigate the non- medical use of drugs, spent several hours with a mem- ber of the Beatles, his wife and a Toronto music concert promoter and smoked...obsessive feeling of guilt? The drug therapist, like the cancer 69 specialist, customarily fails; for them this is hard because people do not forgive...products throughout the national territory: opium (1.856 kg), morphine (1.266 kg, 34 ampoules), heroin (103.481 kg), cocaine (2.16 kg), cannabis
Colombia: Gateway to Defeating Transnational Hell in the Western Hemisphere

DTIC Science & Technology

2004-03-19

Hemisphere through addiction , violence, and corruption.” - General Barry R. McCaffrey This paper addresses the threat to US National security interests posed...million addicts living in the U.S., illicit drugs can be defined as a Weapons of Mass Destruction (WMD).1 The ruinous effects of illicit drugs, 52,000...cheap opium, China suffered pandemic drug addiction . The government, incapable of stopping the addiction , was helpless and by the early 1900’s over half

Translations on Narcotics and Dangerous Drugs, Number 278

DTIC Science & Technology

1976-12-30

present. Cabinet’s decision was announced yesterday by the Minister for business and consumer affairs, Mr Howard, who said the new penalties would be im...BEHIND OPIUM TRAFFICKING Rangoon BOTATAUNG in Burmese 13 Dec 76 p 5 BK /Article by Ye Mya Win: "The Communist Party of Burma Is Doing Good Business ...Lashio, Kunlong and Muse have then sent out their men to buy these goods for redistribution. There is also another business : brandishing their arms
Project CHECO Southeast Asia Report. COIN in Thailand, January 1969 - December 1970

DTIC Science & Technology

1971-07-01

6,000 Chinese troops were living in the areas where Burma, Laos, and Thailand meet, with an estimated 3,000 in Chiang Rai and Chiang Mai provinces of...Consequently, Thai parliament members from Chiang Rai and Chiang Mai complained to the govern- ment about the Chinese opium farming and urged the use...in September 1970 and, after several months of preparation, units were moved to staging areas in Chiang Mai province and later trucked to assembly
Winning the War on Drugs in Mexico? Toward an Integrated Approach to the Illegal Drug Trade

DTIC Science & Technology

2009-12-01

the beginning of the twentieth century when prohibition of the opium trade started. Since then, the social harm of the illegal drug trade in all...its forms has been constantly increasing. Today, the most obvious example of the social harm of the illegal drug trade in Mexico is drug-related crime...reduction approach that has proved ineffective both in Mexico and around the world over the last century because it is not aimed at the social roots of
Decade of Venezuela’s President Hugo Chavez, Por Ahora

DTIC Science & Technology

2009-04-01

minor production source of opium and cocoa , Venezuela is important in the transit of narcotics between Columbia and the US. 60 61 Mindful of this, a...took over.91 To highlight the significance of oil to Venezuela , in 2006, oil represented 91% of its exports compared to 80% five years earlier.92...methodology to examine the last ten years of Venezuelas Hugo Chavez presidency and the significant aspects in terms of US security. The paper contents
A Shared Burden: The Military and Civilian Consequences of Army Pain Management Since 2001

DTIC Science & Technology

2015-08-01

soldiers choosing to begin taking opioids from a lack of discipline. 3 While illegal recreational drugs such as marijuana or cocaine historically have been...23.3 percent indicated they did not know, or had no opinion, may well be related to the lack of information pro - vided to Army unit leaders about...Army soldiers during the Vietnam War used marijuana , and 45% tried narcotics (34% used heroin; 38% used opium.)41 The post-Vietnam Army was ill
Unpacking intoxication, racialising disability.

PubMed

Chen, Mel Y

2015-06-01

This article examines concepts whose strictly medical applications have only partly informed their widespread use and suggests that demonstrably shared logics motivate our thinking across domains in the interest of a politically just engagement. It considers exchanges between the culturally complex concepts of 'toxicity' and 'intoxication', assessing the racialised conditions of their animation in several geopolitically--and quite radically--distinct scenarios. First, the article sets the framework through considering the racial implications of impairment and disability language of 'non-toxic' finance capital in the contemporary US financial crisis. Shifting material foci from 'illiquid financial bodies' to opiates while insisting that neither is 'more' metaphorically toxic than the other, the article turns to address the role of opium and temporality in the interanimations of race and disability in two sites of 19th-century British empire: Langdon Down's clinic for idiocy, and China's retort on opium to Queen Victoria. The article concludes with a provocation that suggests yet another crossing of borders, that between researcher and researched: 'intoxicated method' is a hypothetical mode of approach that refuses idealised research positions by 'critically disabling' the idealised cognitive and conceptual lens of analysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Association of socioeconomic status with consumption of cigarettes, illicit drugs, and alcohol.

PubMed

Marzban, Maryam; Hadji, Maryam; Gholipour, Mahin; Rashidian, Hamideh; Rezaianzadeh, Abbas; Hasanzadeh, Jafar; Haghdoost, Ali Akbar; Rahimi-Movaghar, Afarin; Ghiasvand, Reza; Moradi, Abdolvahab; Khavari-Daneshvar, Hossein; Weiderpass, Elisabete; Kamangar, Farin; Zendehdel, Kazem

2017-08-18

Socioeconomic Status (SES) is considered as one of the important factors associated with use of various drugs. The present study aimed to investigate the effect of SES on cigarette smoking, alcohol use, drug use, and passive exposure to opium and cigarette smoke. In this study, which is part of a multicenter case-control study, the research hypothesis was checked among controls who had referred to hospitals. Data were collected through a questionnaire and laboratory tests to determine the actual consumers of opium and other illicit drugs. Then, the data were analyzed using STATA 13. This study was performed on 364 individuals within the age range of 30 to 75 years. More than 55% of the participants had a history of life-time consumption of cigarettes and hookah as well as alcohol and drugs. The results revealed an inverse relationship between SES and life-time consumption of hookah and alcohol. Furthermore, individuals with higher SES were more likely to deny their drug use. The results revealed little robust evidence supporting the assumption that SES level can have an important effect on illicit drug use. On the other hand, the participants' characteristics could have a prominent effect on precise evaluation of the relationship between SES and drug use. Further multicenter studies are needed with samples diversified in terms of age and ethnicity to identify these confounding relationships.
Damaged goods: return to sender. A review of the historical medical records of repatriated Chinese miners.

PubMed

Ndlovu, Ntombizodwa; Murray, Jill; Seopela, Simon

2006-01-01

After the Anglo-Boer (South African) War (1899-1902), there was a shortage of unskilled labor on the South African gold mines. Chinese men were imported to make up for the deficit. This article reviews the records of indentured Chinese mine workers examined for repatriation in 1905. The records tell of high proportions of social disorders, respiratory diseases, musculoskeletal disorders, opium addiction, and injury. These reflect the social and physical conditions to which these men were exposed in the mines.
A comparative mass spectrometric study of fatty acids and metals in some seed extracts.

PubMed

Suvar, Sonia Niculina; Bleiziffer, R; Podea, P; Iordache, A; Voica, C; Zgavarogea, R; Culea, M

A major cause of cardiovascular diseases and cancer is diet content, so the optimization of micronutrients in food is very important. Omega-3 fatty acids supplementation for patients had beneficial effects on subjective global assessment score and metabolic profiles. Fatty acids content and the metal ions in different seeds (e.g. linseed, poppy, grape, hemp, nuts, pumpkin, sesame, watermelon, chia) recommended as food supplements, purchased on the Romanian market, were compared. Gas chromatography coupled to mass spectrometry (GC-MS) was used as an excellent technique for fatty acids identification and quantitation, and inductively coupled plasma mass spectrometer (ICP-MS) for analytical measurements of metals.
Coltsfoot as a potential cause of deep vein thrombosis and pulmonary embolism in a patient also consuming kava and blue vervain.

PubMed

Freshour, Jessica E; Odle, Brian; Rikhye, Somi; Stewart, David W

2012-09-01

To report a case of deep vein thrombosis (DVT) with symptomatic pulmonary embolism (PE) possibly associated with the use of coltsfoot, kava, or blue vervain. A 27-year-old white male presented with leg pain and swelling, tachycardia, and pleuritic chest pain. He had no significant medical history. A medication history revealed extensive herbal medication use including: coltsfoot, passionflower, red poppy flower petals, wild lettuce, blue lily flowers, wild dagga flowers, Diviners Three Burning Blend® (comprised of salvia divinorum, blue lily, and wild dagga), kava-kava, St. John's Wort, blue vervain, and Dreamer's Blend® (comprised of Calea zacatechichi, vervain, Entada rheedii, wild lettuce, and Eschscholzia californica). Lower extremity Doppler ultrasound and computed topography (CT) of the chest revealed DVT and PE. A hypercoagulable work-up was negative. The patient was treated with enoxaparin and warfarin and was discharged home. While no distinct agent can be identified as a sole cause of this venous thromboembolic event, coltsfoot could potentially affect coagulation through its effect on vascular endothelial cells as they regulate nitric oxide. Nitric oxide is a known mediator of platelet activity and coagulation, particularly in the pulmonary vasculature. Kava and vervain have estrogenic properties. Of the medications consumed by this self-proclaimed "herbalist," coltsfoot is a potential cause of venous thromboembolic disease (VTE).
Neglected foreign body aspiration mimicking bronchial carcinoma.

PubMed

Afghani, Reza; Khandashpour Ghomi, Mahmoud; Khandoozi, Seyed Reza; Yari, Behrouz

2016-07-01

Foreign body aspiration can occur in any age group, but it is more commonly seen in children. In adults, there is usually a predisposing condition that poses a risk of aspiration. If aspiration occurs, prompt diagnosis and extraction of the foreign body is needed to prevent early and late complications. We report a rare case of neglected foreign body aspiration in a 45-year-old schizophrenic opium addicted patient, which resulted in an occlusive lesion in the bronchus, mimicking bronchial carcinoma. © The Author(s) 2016.
Reprogramming of single-cell derived mesenchymal stem cells into hair cell-like cells

PubMed Central

Lin, Zhaoyu; Perez, Philip; Sun, Zhenyu; Liu, Jan-Jan; Shin, June Ho; Hyrc, Krzysztof L.; Samways, Damien; Egan, Terry; Holley, Matthew C.; Bao, Jianxin

2012-01-01

Hypothesis Adult mesenchymal stem cells (MSCs) can be converted into hair cell-like cells by transdetermination. Background Given the fundamental role sensory hair cells play in sound detection and the irreversibility of their loss in mammals, much research has focused on developing methods to generate new hair cells as a means of treating permanent hearing loss. Although MSCs can differentiate into multiple cell lineages, no efficient means of reprogramming them into sensory hair cells exists. Earlier work has shown that the transcription factor Atoh1 is necessary for early development of hair cells, but it is not clear whether Atoh1 can be used to convert MSCs into hair cells. Methods Clonal MSC cell lines were established and reprogrammed into hair cell-like cells by a combination of protein transfer, adenoviral based gene transfer and co-culture with neurons. During transdetermination, inner ear molecular markers were analyzed by RT-PCR, and cell structures were examined by immunocytochemistry. Results Atoh1 overexpression in MSCs failed to convert MSCs into hair cell-like cells, suggesting that the ability of Atoh1 to induce hair cell differentiation is context dependent. Because Atoh1 overexpression successfully transforms VOT-E36 cells into hair cell-like cells, we modified the cell context of MSCs by performing a total protein transfer from VOT-E36 cells prior to overexpressing Atoh1. The modified MSCs were transformed into hair cell-like cells and attracted contacts from spiral ganglion neurons in a co-culture model. Conclusion We established a new procedure, consisting of VOT-E36 protein transfer, Atoh1 overexpression, and co-culture with spiral ganglion neurons, which can transform MSCs into hair cell-like cells. PMID:23111404
Drug addicts seeking treatment after the Iranian Revolution: a clinic-based study.

PubMed

Dalvand, S; Agahi, C; Spencer, C

1984-09-01

A sample survey of 200 addicts attending the Rehabilitation Centre at Shiraz was conducted after the 1979 Iranian Revolution had disrupted both drug supply and addict treatment programmes. The study showed that clinics were, after the revolution, seeing a broader social range of addicts than before; and that action by the authorities was bringing many recently-addicted individuals to clinics. Heroin use predominated among those who were urban residents, whilst villagers were more likely to be opium users. The survey also sought the addicts' perceptions of the reasons for their initiation and addiction.
Genetic toxicology of abused drugs: a brief review.

PubMed

Li, J H; Lin, L F

1998-11-01

Although numerous studies have been conducted on abused drugs, most focus on the problems of addiction (dependence) and their neurotoxicities. Now accumulated data have demonstrated that the genotoxicity and/or carcinogenicity of abused drugs can also be detrimental to our health. In this review, commonly abused substances, including LSD, opiates (diacetylmorphine, morphine, opium and codeine), cocaine, cannabis, betel quid and khat, are discussed for their potential genotoxicity/carcinogenicity. The available literature in the field, although not as abundant as for neurotoxicity, clearly indicates the capability of abused drugs to induce genotoxicity.
CHANGING PATTERN OF DRUG ABUSE AMONG PATIENTS ATTENDING DE-ADDICTION CENTRE AT FARIDKOT

PubMed Central

Sachadev, Jaswant Singh; Yakhmi, Ranvir Singh; Sharma, Ajay Kumar

2002-01-01

Prevalence and patten of drug abuse among patients attending deaddiction centre of GGS Medical College and Hospital Faridkot in the year 1994 were analysed and compared with pattern of drug abuse among the patients attending the same centre in 1998 It was observed that there was an increase in the patients using the drugs available over the counter with chemists. It was also found that there was a decrease in the number of patients using raw opium in the year 1998 as compared to the year 1994. PMID:21206599
Eukaryotic cells and their cell bodies: Cell Theory revised.

PubMed

Baluska, Frantisek; Volkmann, Dieter; Barlow, Peter W

2004-07-01

Cell Theory, also known as cell doctrine, states that all eukaryotic organisms are composed of cells, and that cells are the smallest independent units of life. This Cell Theory has been influential in shaping the biological sciences ever since, in 1838/1839, the botanist Matthias Schleiden and the zoologist Theodore Schwann stated the principle that cells represent the elements from which all plant and animal tissues are constructed. Some 20 years later, in a famous aphorism Omnis cellula e cellula, Rudolf Virchow annunciated that all cells arise only from pre-existing cells. General acceptance of Cell Theory was finally possible only when the cellular nature of brain tissues was confirmed at the end of the 20th century. Cell Theory then rapidly turned into a more dogmatic cell doctrine, and in this form survives up to the present day. In its current version, however, the generalized Cell Theory developed for both animals and plants is unable to accommodate the supracellular nature of higher plants, which is founded upon a super-symplasm of interconnected cells into which is woven apoplasm, symplasm and super-apoplasm. Furthermore, there are numerous examples of multinucleate coenocytes and syncytia found throughout the eukaryote superkingdom posing serious problems for the current version of Cell Theory. To cope with these problems, we here review data which conform to the original proposal of Daniel Mazia that the eukaryotic cell is composed of an elemental Cell Body whose structure is smaller than the cell and which is endowed with all the basic attributes of a living entity. A complement to the Cell Body is the Cell Periphery Apparatus, which consists of the plasma membrane associated with other periphery structures. Importantly, boundary structures of the Cell Periphery Apparatus, although capable of some self-assembly, are largely produced and maintained by Cell Body activities and can be produced from it de novo. These boundary structures serve not only as
Eukaryotic Cells and their Cell Bodies: Cell Theory Revised

PubMed Central

BALUŠKA, FRANTIŠEK; VOLKMANN, DIETER; BARLOW, PETER W.

2004-01-01

• Background Cell Theory, also known as cell doctrine, states that all eukaryotic organisms are composed of cells, and that cells are the smallest independent units of life. This Cell Theory has been influential in shaping the biological sciences ever since, in 1838/1839, the botanist Matthias Schleiden and the zoologist Theodore Schwann stated the principle that cells represent the elements from which all plant and animal tissues are constructed. Some 20 years later, in a famous aphorism Omnis cellula e cellula, Rudolf Virchow annunciated that all cells arise only from pre‐existing cells. General acceptance of Cell Theory was finally possible only when the cellular nature of brain tissues was confirmed at the end of the 20th century. Cell Theory then rapidly turned into a more dogmatic cell doctrine, and in this form survives up to the present day. In its current version, however, the generalized Cell Theory developed for both animals and plants is unable to accommodate the supracellular nature of higher plants, which is founded upon a super‐symplasm of interconnected cells into which is woven apoplasm, symplasm and super‐apoplasm. Furthermore, there are numerous examples of multinucleate coenocytes and syncytia found throughout the eukaryote superkingdom posing serious problems for the current version of Cell Theory. • Scope To cope with these problems, we here review data which conform to the original proposal of Daniel Mazia that the eukaryotic cell is composed of an elemental Cell Body whose structure is smaller than the cell and which is endowed with all the basic attributes of a living entity. A complement to the Cell Body is the Cell Periphery Apparatus, which consists of the plasma membrane associated with other periphery structures. Importantly, boundary stuctures of the Cell Periphery Apparatus, although capable of some self‐assembly, are largely produced and maintained by Cell Body activities and can be produced from it de novo. These
Cell Adhesions: Actin-Based Modules that Mediate Cell-Extracellular Matrix and Cell-Cell Interactions

PubMed Central

Bachir, Alexia; Horwitz, Alan Rick; Nelson, W. James; Bianchini, Julie M.

2018-01-01

Cell adhesions link cells to the extracellular matrix (ECM) and to each other, and depend on interactions with the actin cytoskeleton. Both cell-ECM and cell-cell adhesion sites contain discrete, yet overlapping functional modules. These modules establish physical association with the actin cytoskeleton, locally modulate actin organization and dynamics, and trigger intracellular signaling pathways. Interplay between these modules generates distinct actin architectures that underlie different stages, types, and functions of cell-ECM and cell-cell adhesions. Actomyosin contractility is required to generate mature, stable adhesions, as well as sense and translate the mechanical properties of the cellular environment to changes in cell organization and behavior. In this chapter we discuss the organization and function of different adhesion modules and how they interact with the actin cytoskeleton. We highlight the molecular mechanisms of mechanotransduction in adhesions, and how adhesion molecules mediate crosstalk between cell-ECM and cell-cell adhesion sites. PMID:28679638
Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Felthaus, O.; Department of Oral and Maxillofacial Surgery, University of Regensburg; Ettl, T.

2011-04-01

Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simplemore » method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.« less
Cell-to-Cell Transmission Can Overcome Multiple Donor and Target Cell Barriers Imposed on Cell-Free HIV

PubMed Central

Ilinskaya, Anna; Dorjbal, Batsukh; Truong, Rosaline; Derse, David; Uchil, Pradeep D.; Heidecker, Gisela; Mothes, Walther

2013-01-01

Virus transmission can occur either by a cell-free mode through the extracellular space or by cell-to-cell transmission involving direct cell-to-cell contact. The factors that determine whether a virus spreads by either pathway are poorly understood. Here, we assessed the relative contribution of cell-free and cell-to-cell transmission to the spreading of the human immunodeficiency virus (HIV). We demonstrate that HIV can spread by a cell-free pathway if all the steps of the viral replication cycle are efficiently supported in highly permissive cells. However, when the cell-free path was systematically hindered at various steps, HIV transmission became contact-dependent. Cell-to-cell transmission overcame barriers introduced in the donor cell at the level of gene expression and surface retention by the restriction factor tetherin. Moreover, neutralizing antibodies that efficiently inhibit cell-free HIV were less effective against cell-to-cell transmitted virus. HIV cell-to-cell transmission also efficiently infected target T cells that were relatively poorly susceptible to cell-free HIV. Importantly, we demonstrate that the donor and target cell types influence critically the extent by which cell-to-cell transmission can overcome each barrier. Mechanistically, cell-to-cell transmission promoted HIV spread to more cells and infected target cells with a higher proviral content than observed for cell-free virus. Our data demonstrate that the frequently observed contact-dependent spread of HIV is the result of specific features in donor and target cell types, thus offering an explanation for conflicting reports on the extent of cell-to-cell transmission of HIV. PMID:23308151

Meningeal mast cell-T cell crosstalk regulates T cell encephalitogenicity.

PubMed

Russi, Abigail E; Walker-Caulfield, Margaret E; Guo, Yong; Lucchinetti, Claudia F; Brown, Melissa A

2016-09-01

GM-CSF is a cytokine produced by T helper (Th) cells that plays an essential role in orchestrating neuroinflammation in experimental autoimmune encephalomyelitis, a rodent model of multiple sclerosis. Yet where and how Th cells acquire GM-CSF expression is unknown. In this study we identify mast cells in the meninges, tripartite tissues surrounding the brain and spinal cord, as important contributors to antigen-specific Th cell accumulation and GM-CSF expression. In the absence of mast cells, Th cells do not accumulate in the meninges nor produce GM-CSF. Mast cell-T cell co-culture experiments and selective mast cell reconstitution of the meninges of mast cell-deficient mice reveal that resident meningeal mast cells are an early source of caspase-1-dependent IL-1β that licenses Th cells to produce GM-CSF and become encephalitogenic. We also provide evidence of mast cell-T cell co-localization in the meninges and CNS of recently diagnosed acute MS patients indicating similar interactions may occur in human demyelinating disease. Copyright © 2016 Elsevier Ltd. All rights reserved.
Engineering Cell-Cell Signaling

PubMed Central

Milano, Daniel F.; Natividad, Robert J.; Asthagiri, Anand R.

2014-01-01

Juxtacrine cell-cell signaling mediated by the direct interaction of adjoining mammalian cells is arguably the mode of cell communication that is most recalcitrant to engineering. Overcoming this challenge is crucial for progress in biomedical applications, such as tissue engineering, regenerative medicine, immune system engineering and therapeutic design. Here, we describe the significant advances that have been made in developing synthetic platforms (materials and devices) and synthetic cells (cell surface engineering and synthetic gene circuits) to modulate juxtacrine cell-cell signaling. In addition, significant progress has been made in elucidating design rules and strategies to modulate juxtacrine signaling based on quantitative, engineering analysis of the mechanical and regulatory role of juxtacrine signals in the context of other cues and physical constraints in the microenvironment. These advances in engineering juxtacrine signaling lay a strong foundation for an integrative approach to utilizing synthetic cells, advanced ‘chassis’ and predictive modeling to engineer the form and function of living tissues. PMID:23856592
Mast cells enhance T cell activation: Importance of mast cell-derived TNF

NASA Astrophysics Data System (ADS)

Nakae, Susumu; Suto, Hajime; Kakurai, Maki; Sedgwick, Jonathon D.; Tsai, Mindy; Galli, Stephen J.

2005-05-01

Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production. allergy | asthma | autoimmunity | cytokines | immune response
Esophageal Cancer in Golestan Province, Iran: A Review of Genetic Susceptibility and Environmental Risk Factors

PubMed Central

Gholipour, Mahin; Islami, Farhad; Roshandel, Gholamreza; Khoshnia, Masoud; Badakhshan, Abbas; Moradi, Abdolvahab; Malekzadeh, Reza

2016-01-01

Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor that is typically diagnosed only when the tumor has gained remarkable size, extended to peripheral tissues, and led to dysphagia. Five-year survival of advanced cancer is still very poor (19%), even with improved surgical techniques and adjuvant chemoradiation therapy. Therefore, early detection and prevention are the most important strategies to reduce the burden of ESCC. Our review will focus on the studies conducted in Golestan province, an area with a high prevalence of ESCC in northern Iran. We review three aspects of the research literature on ESCC: epidemiological features, environmental factors (including substance abuse, environmental contaminants, dietary factors, and human papillomavirus [HPV]), and molecular factors (including oncogenes, tumor suppressor genes, cell cycle regulatory proteins, and other relevant biomarkers). Epidemiological and experimental data suggest that some chemicals and lifestyle factors, including polycyclic aromatic hydrocarbons (PAHs), cigarette smoking, opium use, and hot tea drinking are associated with the development of ESCC in Golestan. HPV infects the esophageal epithelium, but so far, no firm evidence of its involvement in esophageal carcinogenesis has been provided. Some of these factors, notably hot tea drinking, may render the esophageal mucosa more susceptible to injury by other carcinogens. There are few studies at molecular level on ESCC in Golestan. Increasing awareness about the known risk factors of ESCC could potentially reduce the burden of ESCC in the region. Further studies on risk factors, identifying high risk populations, and early detection are needed. PMID:27957288
[The cell theory. Progress in studies on cell-cell communications].

PubMed

Brodskiĭ, V Ia

2009-01-01

Current data confirm the fundamental statement of the cell theory concerning the cell reproduction in a series of generations (omnis cellula e cellula). Cell communities or ensembles integrated by the signaling systems established in prokaryotes and protists and functioning in multicellular organisms including mammals are considered as the structural and functional unit of a multicellular organism. The cell is an elementary unit of life and basis of organism development and functioning. At the same time, the adult organism is not just a totality of cells. Multinucleated cells in some tissues, syncytial structure, and structural-functional units of organs are adaptations for optimal functioning of the multicellular organism and manifestations of cell-cell communications in development and definitive functioning. The cell theory was supplemented and developed by studies on cell-cell communications; however, these studies do not question the main generalizations of the theory.
Investigating cell-substrate and cell-cell interactions by means of single-cell-probe force spectroscopy.

PubMed

Moreno-Cencerrado, Alberto; Iturri, Jagoba; Pecorari, Ilaria; D M Vivanco, Maria; Sbaizero, Orfeo; Toca-Herrera, José L

2017-01-01

Cell adhesion forces are typically a mixture of specific and nonspecific cell-substrate and cell-cell interactions. In order to resolve these phenomena, Atomic Force Microscopy appears as a powerful device which can measure cell parameters by means of manipulation of single cells. This method, commonly known as cell-probe force spectroscopy, allows us to control the force applied, the area of interest, the approach/retracting speed, the force rate, and the time of interaction. Here, we developed a novel approach for in situ cantilever cell capturing and measurement of specific cell interactions. In particular, we present a new setup consisting of two different half-surfaces coated either with recrystallized SbpA bacterial cell surface layer proteins (S-layers) or integrin binding Fibronectin, on which MCF-7 breast cancer cells are incubated. The presence of a clear physical boundary between both surfaces benefits for a quick detection of the region under analysis. Thus, quantitative results about SbpA-cell and Fibronectin-cell adhesion forces as a function of the contact time are described. Additionally, the importance of the cell spreading in cell-cell interactions has been studied for surfaces coated with two different Fibronectin concentrations: 20 μg/mL (FN20) and 100 μg/mL (FN100), which impact the number of substrate receptors. Microsc. Res. Tech. 80:124-130, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Molluscan cells in culture: primary cell cultures and cell lines

PubMed Central

Yoshino, T. P.; Bickham, U.; Bayne, C. J.

2013-01-01

In vitro cell culture systems from molluscs have significantly contributed to our basic understanding of complex physiological processes occurring within or between tissue-specific cells, yielding information unattainable using intact animal models. In vitro cultures of neuronal cells from gastropods show how simplified cell models can inform our understanding of complex networks in intact organisms. Primary cell cultures from marine and freshwater bivalve and gastropod species are used as biomonitors for environmental contaminants, as models for gene transfer technologies, and for studies of innate immunity and neoplastic disease. Despite efforts to isolate proliferative cell lines from molluscs, the snail Biomphalaria glabrata Say, 1818 embryonic (Bge) cell line is the only existing cell line originating from any molluscan species. Taking an organ systems approach, this review summarizes efforts to establish molluscan cell cultures and describes the varied applications of primary cell cultures in research. Because of the unique status of the Bge cell line, an account is presented of the establishment of this cell line, and of how these cells have contributed to our understanding of snail host-parasite interactions. Finally, we detail the difficulties commonly encountered in efforts to establish cell lines from molluscs and discuss how these difficulties might be overcome. PMID:24198436
Size Estimation of Groups at High Risk of HIV/AIDS using Network Scale Up in Kerman, Iran

PubMed Central

Shokoohi, Mostafa; Baneshi, Mohammad Reza; Haghdoost, Ali-Akbar

2012-01-01

Objective: To estimate the size of groups at high risk of HIV, Network Scale UP (NSU), an indirect method, was used. Methods: 500 Kermanian male aged 18 to 45 were recruited. 8 groups at high risk of HIV were defined: Users of opium, unknown drug, ecstasy, and alcohol; intra-venous drug users (IDUs; males who have extra-marital sex with females (MSF); male who have sex with female sex workers (MFSW); and male who have sex with other male (MSMs). We asked respondents whether they know anybody (probability method), and if yes, how many people (frequency method) in our target groups. Results: Estimates derived in the probability method were higher than the frequency method. Based on the probability method, 13.7% (95% CI: 11.3%, 16.1%) of males used alcohol at least once in last year; the corresponding percent for opium was 13.1% (95% CI: 10.9%, 15.3%). In addition, 12% has extra-marital sex in last year (95% CI: 10%, 14%); while 7% (95% CI: 5.8%, 8.2%) had sex with a female sex worker. Conclusion: We showed that drug use is more common among young and mid-age males; although their sexual contacts were also considerable. These percentages show that special preventive program is needed to control an HIV transmission. Estimates derived from probability method were comparable with data from external sources. The underestimation in frequency method might be due to the fact that respondents are not aware of sensitive characteristics of all those in their network and underreporting is likely to occur. PMID:22891148
An indirect estimation of the population size of students with high-risk behaviors in select universities of medical sciences: A network scale-up study.

PubMed

Sajjadi, Homeira; Jorjoran Shushtari, Zahra; Shati, Mohsen; Salimi, Yahya; Dejman, Masoomeh; Vameghi, Meroe; Karimi, Salahedin; Mahmoodi, Zohreh

2018-01-01

Network scale-up is one of the most important indirect methods of estimating the size of clandestine populations and people with high-risk behaviors. The present study is an indirect estimation of the population size of students with high-risk behaviors in select universities of medical sciences. A total of 801 students from two University of Medical Sciences at Tehran and Alborz University of Medical Sciences were selected through convenience sampling. Six subgroups of high-risk behaviors were examined in the study, including Tramadol use, cannabis use, opium use, alcohol consumption, extramarital heterosexual intercourse, and heterosexual intercourse in return for money. To estimate the social network size in the study population, each participant was asked to name their close student friends from the two select universities. Data were collected using a checklist designed for this purpose. The participants' mean number of close friends from the selected medical universities was C = 8.14 (CI: 7.54-8.75). Within these social networks, friends with extramarital heterosexual intercourse (5.53%) and friends who consumed alcohol (4.92%) had the highest frequency, and friends who used opium (0.33%) had the lowest frequency. The variables of age, gender, marital status, type of residence and academic degree were significantly related to the likelihood of having close friends with certain high-risk behaviors (P<0.001). According to the results obtained, alcohol consumption and extramarital heterosexual intercourse are very common among students. Special HIV prevention programs are therefore necessary for this age group.
Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.

PubMed

Feyerabend, Thorsten B; Terszowski, Grzegorz; Tietz, Annette; Blum, Carmen; Luche, Hervé; Gossler, Achim; Gale, Nicholas W; Radtke, Freddy; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2009-01-16

Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.
Glioma cell dispersion is driven by α5 integrin-mediated cell-matrix and cell-cell interactions.

PubMed

Blandin, Anne-Florence; Noulet, Fanny; Renner, Guillaume; Mercier, Marie-Cécile; Choulier, Laurence; Vauchelles, Romain; Ronde, Philippe; Carreiras, Franck; Etienne-Selloum, Nelly; Vereb, Gyorgy; Lelong-Rebel, Isabelle; Martin, Sophie; Dontenwill, Monique; Lehmann, Maxime

2016-07-01

Glioblastoma multiform (GBM) is the most common and most aggressive primary brain tumor. The fibronectin receptor, α5 integrin is a pertinent novel therapeutic target. Despite numerous data showing that α5 integrin support tumor cell migration and invasion, it has been reported that α5 integrin can also limit cell dispersion by increasing cell-cell interaction. In this study, we showed that α5 integrin was involved in cell-cell interaction and gliomasphere formation. α5-mediated cell-cell cohesion limited cell dispersion from spheroids in fibronectin-poor microenvironment. However, in fibronectin-rich microenvironment, α5 integrin promoted cell dispersion. Ligand-occupied α5 integrin and fibronectin were distributed in fibril-like pattern at cell-cell junction of evading cells, forming cell-cell fibrillar adhesions. Activated focal adhesion kinase was not present in these adhesions but was progressively relocalized with α5 integrin as cell migrates away from the spheroids. α5 integrin function in GBM appears to be more complex than previously suspected. As GBM overexpressed fibronectin, it is most likely that in vivo, α5-mediated dissemination from the tumor mass overrides α5-mediated tumor cell cohesion. In this respect, α5-integrin antagonists may be useful to limit GBM invasion in brain parenchyma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Border cell release: Cell separation without cell wall degradation?

PubMed

Mravec, Jozef

2017-07-03

Plant border cells are specialized cells derived from the root cap with roles in the biomechanics of root growth and in forming a barrier against pathogens. The mechanism of highly localized cell separation which is essential for their release to the environment is little understood. Here I present in situ analysis of Brachypodium distachyon, a model organism for grasses which possess type II primary cell walls poor in pectin content. Results suggest similarity in spatial dynamics of pectic homogalacturonan during dicot and monocot border cell release. Integration of observations from different species leads to the hypothesis that this process most likely does not involve degradation of cell wall material but rather uses unique cell wall structural and compositional means enabling both the rigidity of the root cap as well as detachability of given cells on its surface.
Cell-cell interactions mediate cytoskeleton organization and collective endothelial cell chemotaxis.

PubMed

Shamloo, Amir

2014-09-01

This study investigates the role of cell-cell and cell-ligand interactions in cytoskeleton organization of endothelial cells (ECs) and their directional migration within a microfluidic device. The migration of ECs in response to a biochemical factor was studied. Mathematical analysis of the cell migration pathways and cellular cytoskeleton revealed that directional migration, migration persistence length, migration speed, and cytoskeletal stress fiber alignment can be mediated by the level of cell contacts as well as the presence or absence of a biochemical polarizing factor. It was shown that in the presence of a biochemical polarizing factor, higher cell density and more frequent cell contacts has a reinforcing effect on collective cell chemotaxis. In contrast, in the absence of a polarizing factor, high cell density can decrease or suppress the ability of the cells to migrate. Also, the correlation of actin stress fiber organization and alignment with directional migration of ECs was investigated. It was shown that in the presence of a biochemical polarizing factor, stress fibers within the cytoskeleton of ECs can be significantly aligned parallel to the gradient direction when the cells have higher level of contacts. The results also show that the organization and alignment of actin stress fibers is mediated by cell adhesion junctions during collective cell migration and introduce cell-cell interactions as a key factor during collective cell chemotaxis. © 2014 Wiley Periodicals, Inc.
Cell Cycle Related Differentiation of Bone Marrow Cells into Lung Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dooner, Mark; Aliotta, Jason M.; Pimental, Jeffrey

2007-12-31

Green-fluorescent protein (GFP) labeled marrow cells transplanted into lethally irradiated mice can be detected in the lungs of transplanted mice and have been shown to express lung specific proteins while lacking the expression of hematopoietic markers. We have studied marrow cells induced to transit cell cycle by exposure to IL-3, IL-6, IL-11 and steel factor at different times of culture corresponding to different phases of cell cycle. We have found that marrow cells at the G1/S interface have a 3-fold increase in cells which assume a lung phenotype and that this increase is no longer seen in late S/G2. Thesemore » cells have been characterized as GFP{sup +} CD45{sup -} and GFP{sup +} cytokeratin{sup +}. Thus marrow cells with the capacity to convert into cells with a lung phenotype after transplantation show a reversible increase with cytokine induced cell cycle transit. Previous studies have shown the phenotype of bone marrow stem cells fluctuates reversibly as these cells traverse cell cycle, leading to a continuum model of stem cell regulation. The present studies indicate that marrow stem cell production of nonhematopoietic cells also fluctuates on a continuum.« less
Cell wars: regulation of cell survival and proliferation by cell competition

PubMed Central

Vivarelli, Silvia; Wagstaff, Laura; Piddini, Eugenia

2012-01-01

During cell competition fitter cells take over the tissue at the expense of viable, but less fit, cells, which are eliminated by induction of apoptosis or senescence. This probably acts as a quality-control mechanism to eliminate suboptimal cells and safeguard organ function. Several experimental conditions have been shown to trigger cell competition, including differential levels in ribosomal activity or in signalling pathway activation between cells, although it is unclear how those differences are sensed and translated into fitness levels. Many of the pathways implicated in cell competition have been previously linked with cancer, and this has led to the hypothesis that cell competition could play a role in tumour formation. Cell competition could be co-opted by cancer cells to kill surrounding normal cells and boost their own tissue colonization. However, in some cases, cell competition could have a tumour suppressor role, as cells harbouring mutations in a subset of tumour suppressor genes are killed by wild-type cells. Originally described in developing epithelia, competitive interactions have also been observed in some stem cell niches, where they play a role in regulating stem cell selection, maintenance and tissue repopulation. Thus competitive interactions could be relevant to the maintenance of tissue fitness and have a protective role against aging. PMID:22928509
Quantitative Characterization of Cell Behaviors through Cell Cycle Progression via Automated Cell Tracking

PubMed Central

Wang, Yuliang; Jeong, Younkoo; Jhiang, Sissy M.; Yu, Lianbo; Menq, Chia-Hsiang

2014-01-01

Cell behaviors are reflections of intracellular tension dynamics and play important roles in many cellular processes. In this study, temporal variations in cell geometry and cell motion through cell cycle progression were quantitatively characterized via automated cell tracking for MCF-10A non-transformed breast cells, MCF-7 non-invasive breast cancer cells, and MDA-MB-231 highly metastatic breast cancer cells. A new cell segmentation method, which combines the threshold method and our modified edge based active contour method, was applied to optimize cell boundary detection for all cells in the field-of-view. An automated cell-tracking program was implemented to conduct live cell tracking over 40 hours for the three cell lines. The cell boundary and location information was measured and aligned with cell cycle progression with constructed cell lineage trees. Cell behaviors were studied in terms of cell geometry and cell motion. For cell geometry, cell area and cell axis ratio were investigated. For cell motion, instantaneous migration speed, cell motion type, as well as cell motion range were analyzed. We applied a cell-based approach that allows us to examine and compare temporal variations of cell behavior along with cell cycle progression at a single cell level. Cell body geometry along with distribution of peripheral protrusion structures appears to be associated with cell motion features. Migration speed together with motion type and motion ranges are required to distinguish the three cell-lines examined. We found that cells dividing or overlapping vertically are unique features of cell malignancy for both MCF-7 and MDA-MB-231 cells, whereas abrupt changes in cell body geometry and cell motion during mitosis are unique to highly metastatic MDA-MB-231 cells. Taken together, our live cell tracking system serves as an invaluable tool to identify cell behaviors that are unique to malignant and/or highly metastatic breast cancer cells. PMID:24911281
Mesenchymal stem cell like (MSCl) cells generated from human embryonic stem cells support pluripotent cell growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Varga, Nora; Vereb, Zoltan; Rajnavoelgyi, Eva

2011-10-28

Highlights: Black-Right-Pointing-Pointer MSC like cells were derived from hESC by a simple and reproducible method. Black-Right-Pointing-Pointer Differentiation and immunosuppressive features of MSCl cells were similar to bmMSC. Black-Right-Pointing-Pointer MSCl cells as feeder cells support the undifferentiated growth of hESC. -- Abstract: Mesenchymal stem cell like (MSCl) cells were generated from human embryonic stem cells (hESC) through embryoid body formation, and isolated by adherence to plastic surface. MSCl cell lines could be propagated without changes in morphological or functional characteristics for more than 15 passages. These cells, as well as their fluorescent protein expressing stable derivatives, efficiently supported the growth ofmore » undifferentiated human embryonic stem cells as feeder cells. The MSCl cells did not express the embryonic (Oct4, Nanog, ABCG2, PODXL, or SSEA4), or hematopoietic (CD34, CD45, CD14, CD133, HLA-DR) stem cell markers, while were positive for the characteristic cell surface markers of MSCs (CD44, CD73, CD90, CD105). MSCl cells could be differentiated toward osteogenic, chondrogenic or adipogenic directions and exhibited significant inhibition of mitogen-activated lymphocyte proliferation, and thus presented immunosuppressive features. We suggest that cultured MSCl cells can properly model human MSCs and be applied as efficient feeders in hESC cultures.« less
Single cell RNA sequencing of stem cell-derived retinal ganglion cells.

PubMed

Daniszewski, Maciej; Senabouth, Anne; Nguyen, Quan H; Crombie, Duncan E; Lukowski, Samuel W; Kulkarni, Tejal; Sluch, Valentin M; Jabbari, Jafar S; Chamling, Xitiz; Zack, Donald J; Pébay, Alice; Powell, Joseph E; Hewitt, Alex W

2018-02-13

We used single cell sequencing technology to characterize the transcriptomes of 1,174 human embryonic stem cell-derived retinal ganglion cells (RGCs) at the single cell level. The human embryonic stem cell line BRN3B-mCherry (A81-H7), was differentiated to RGCs using a guided differentiation approach. Cells were harvested at day 36 and prepared for single cell RNA sequencing. Our data indicates the presence of three distinct subpopulations of cells, with various degrees of maturity. One cluster of 288 cells showed increased expression of genes involved in axon guidance together with semaphorin interactions, cell-extracellular matrix interactions and ECM proteoglycans, suggestive of a more mature RGC phenotype.
Rate dependence of cell-to-cell variations of lithium-ion cells.

PubMed

An, Fuqiang; Chen, Lufan; Huang, Jun; Zhang, Jianbo; Li, Ping

2016-10-11

Lithium-ion cells are commonly used in a multicell configuration in power devices and electric vehicles, making the cell-to-cell variation (CtCV) a key factor to consider in system design and management. Previous studies on CtCV have two major limitations: the number of cells is usually less than one hundred, and the cells are usually commercial cells already subjected to cell-screenings. In this article, we first make a statistical analysis on the CtCV of 5473 fresh cells from an automotive battery manufacturer before the cell-screening process. Secondly, 198 cells are randomly selected from these 5473 cells and the rate dependence of the CtCV is examined, focusing on the correlations of capacity versus weight and capacity versus resistance, corresponding to thermodynamic and kinetic factors, respectively. The rate dependence of these two correlations is explained from a phenomenological model. Finally, eight cells from the 198 cells are further characterized with electrochemical impedance spectroscopy method to elucidate the kinetic origins of the CtCV.
Rate dependence of cell-to-cell variations of lithium-ion cells

PubMed Central

An, Fuqiang; Chen, Lufan; Huang, Jun; Zhang, Jianbo; Li, Ping

2016-01-01

Lithium-ion cells are commonly used in a multicell configuration in power devices and electric vehicles, making the cell-to-cell variation (CtCV) a key factor to consider in system design and management. Previous studies on CtCV have two major limitations: the number of cells is usually less than one hundred, and the cells are usually commercial cells already subjected to cell-screenings. In this article, we first make a statistical analysis on the CtCV of 5473 fresh cells from an automotive battery manufacturer before the cell-screening process. Secondly, 198 cells are randomly selected from these 5473 cells and the rate dependence of the CtCV is examined, focusing on the correlations of capacity versus weight and capacity versus resistance, corresponding to thermodynamic and kinetic factors, respectively. The rate dependence of these two correlations is explained from a phenomenological model. Finally, eight cells from the 198 cells are further characterized with electrochemical impedance spectroscopy method to elucidate the kinetic origins of the CtCV. PMID:27725767

Procrastination and Self-Efficacy Among Intravenous Drug Users on a Methadone Maintenance Program in Sari City, Iran, 2013.

PubMed

Taghizadeh, Fatemeh; Yazdani Cherati, Jamshid

2015-12-01

Self-efficacy is the belief that one has the ability to implement the behaviors needed to produce a desired effect. There has been growing interest in the role of self-efficacy as a predictor and/or mediator of treatment outcome in a number of domains. Procrastination is a self-regulatory failure, defined as the voluntary delay of an intended course of action despite expecting to be worse off for the delay. Behavioral procrastination is a self-sabotage strategy that allows people to shift blame and avoid action; the decisional procrastination strategy is to put off making a decision when dealing with conflicts or choices. Procrastination has a great role in quitting drug addiction. The aim of this study was to determine the relationship between procrastination and self-efficacy and other factors among intravenous drug users. This cross-sectional study was conducted on 178 intravenous drug users in the behavioral disease counseling, health center in Sari city, Mazandaran province, Iran, in 2013. The samples were selected through census sampling, descriptive and inferential statistics were used to measure the properties of distribution that depicts a set of data shown as frequency distribution tables, while for the mean and standard deviation, chi-square, Fisher and Spearman-Brown coefficients were used to analyze the data. The mean age of the participants was 43 years. Seventy-two percent of them were married and opium was the first drug used. The first substance used in them was 54% of opium, 33% cannabis and 5% alcohol and 79% smoking. The reason of the first drug use in 32% of the subjects was temptation and in 10% a friend's influence. The mean age of the first drug use was 23 years, and the frequency was 2 times per day. All of them had relapse at least once. Seven percent of them currently use other materials (2% crystal, 5% alcohol and opium and crack) both in methadone treatment. Behavioral procrastination in 60.5% of them and decisional procrastination in
Fragments of Target Cells are Internalized into Retroviral Envelope Protein-Expressing Cells during Cell-Cell Fusion by Endocytosis

PubMed Central

Izumida, Mai; Kamiyama, Haruka; Suematsu, Takashi; Honda, Eri; Koizumi, Yosuke; Yasui, Kiyoshi; Hayashi, Hideki; Ariyoshi, Koya; Kubo, Yoshinao

2016-01-01

Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within. PMID:26834711
9. ENGINE TEST CELL BUILDING INTERIOR. CELL ACCESS ELEVATOR, CELLS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. ENGINE TEST CELL BUILDING INTERIOR. CELL ACCESS ELEVATOR, CELLS 2 AND 4, BASEMENT LEVEL. LOOKING SOUTHEAST. - Fairchild Air Force Base, Engine Test Cell Building, Near intersection of Arnold Street & George Avenue, Spokane, Spokane County, WA
The cell cycle as a brake for β-cell regeneration from embryonic stem cells.

PubMed

El-Badawy, Ahmed; El-Badri, Nagwa

2016-01-13

The generation of insulin-producing β cells from stem cells in vitro provides a promising source of cells for cell transplantation therapy in diabetes. However, insulin-producing cells generated from human stem cells show deficiency in many functional characteristics compared with pancreatic β cells. Recent reports have shown molecular ties between the cell cycle and the differentiation mechanism of embryonic stem (ES) cells, assuming that cell fate decisions are controlled by the cell cycle machinery. Both β cells and ES cells possess unique cell cycle machinery yet with significant contrasts. In this review, we compare the cell cycle control mechanisms in both ES cells and β cells, and highlight the fundamental differences between pluripotent cells of embryonic origin and differentiated β cells. Through critical analysis of the differences of the cell cycle between these two cell types, we propose that the cell cycle of ES cells may act as a brake for β-cell regeneration. Based on these differences, we discuss the potential of modulating the cell cycle of ES cells for the large-scale generation of functionally mature β cells in vitro. Further understanding of the factors that modulate the ES cell cycle will lead to new approaches to enhance the production of functional mature insulin-producing cells, and yield a reliable system to generate bona fide β cells in vitro.
Can mesenchymal cells undergo collective cell migration?

PubMed Central

Theveneau, Eric

2011-01-01

Cell migration is critical for proper development of the embryo and is also used by many cell types to perform their physiological function. For instance, cell migration is essential for immune cells to monitor the body and for epithelial cells to heal a wound whereas, in cancer cells, acquisition of migratory capabilities is a critical step toward malignancy. Migratory cells are often categorized into two groups: (1) mesenchymal cells, produced by an epithelium-to-mesenchyme transition, that undergo solitary migration and (2) epithelial-like cells which migrate collectively. However, on some occasions, mesenchymal cells may travel in large, dense groups and exhibit key features of collectively migrating cells such as coordination and cooperation. Here, using data published on neural crest cells, a highly invasive mesenchymal cell population that extensively migrate throughout the embryo, we explore the idea that mesenchymal cells, including cancer cells, might be able to undergo collective cell migration under certain conditions and discuss how they could do so. PMID:22274714
Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamada, Shin; Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp; Takikawa, Tetsuya

2012-05-04

Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression ofmore » pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called 'cancer stem cells', within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the 'stemness' of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.« less
In silico characterization of cell-cell interactions using a cellular automata model of cell culture.

PubMed

Kihara, Takanori; Kashitani, Kosuke; Miyake, Jun

2017-07-14

Cell proliferation is a key characteristic of eukaryotic cells. During cell proliferation, cells interact with each other. In this study, we developed a cellular automata model to estimate cell-cell interactions using experimentally obtained images of cultured cells. We used four types of cells; HeLa cells, human osteosarcoma (HOS) cells, rat mesenchymal stem cells (MSCs), and rat smooth muscle A7r5 cells. These cells were cultured and stained daily. The obtained cell images were binarized and clipped into squares containing about 10 4 cells. These cells showed characteristic cell proliferation patterns. The growth curves of these cells were generated from the cell proliferation images and we determined the doubling time of these cells from the growth curves. We developed a simple cellular automata system with an easily accessible graphical user interface. This system has five variable parameters, namely, initial cell number, doubling time, motility, cell-cell adhesion, and cell-cell contact inhibition (of proliferation). Within these parameters, we obtained initial cell numbers and doubling times experimentally. We set the motility at a constant value because the effect of the parameter for our simulation was restricted. Therefore, we simulated cell proliferation behavior with cell-cell adhesion and cell-cell contact inhibition as variables. By comparing growth curves and proliferation cell images, we succeeded in determining the cell-cell interaction properties of each cell. Simulated HeLa and HOS cells exhibited low cell-cell adhesion and weak cell-cell contact inhibition. Simulated MSCs exhibited high cell-cell adhesion and positive cell-cell contact inhibition. Simulated A7r5 cells exhibited low cell-cell adhesion and strong cell-cell contact inhibition. These simulated results correlated with the experimental growth curves and proliferation images. Our simulation approach is an easy method for evaluating the cell-cell interaction properties of cells.
Local cell metrics: a novel method for analysis of cell-cell interactions.

PubMed

Su, Jing; Zapata, Pedro J; Chen, Chien-Chiang; Meredith, J Carson

2009-10-23

The regulation of many cell functions is inherently linked to cell-cell contact interactions. However, effects of contact interactions among adherent cells can be difficult to detect with global summary statistics due to the localized nature and noise inherent to cell-cell interactions. The lack of informatics approaches specific for detecting cell-cell interactions is a limitation in the analysis of large sets of cell image data, including traditional and combinatorial or high-throughput studies. Here we introduce a novel histogram-based data analysis strategy, termed local cell metrics (LCMs), which addresses this shortcoming. The new LCM method is demonstrated via a study of contact inhibition of proliferation of MC3T3-E1 osteoblasts. We describe how LCMs can be used to quantify the local environment of cells and how LCMs are decomposed mathematically into metrics specific to each cell type in a culture, e.g., differently-labelled cells in fluorescence imaging. Using this approach, a quantitative, probabilistic description of the contact inhibition effects in MC3T3-E1 cultures has been achieved. We also show how LCMs are related to the naïve Bayes model. Namely, LCMs are Bayes class-conditional probability functions, suggesting their use for data mining and classification. LCMs are successful in robust detection of cell contact inhibition in situations where conventional global statistics fail to do so. The noise due to the random features of cell behavior was suppressed significantly as a result of the focus on local distances, providing sensitive detection of cell-cell contact effects. The methodology can be extended to any quantifiable feature that can be obtained from imaging of cell cultures or tissue samples, including optical, fluorescent, and confocal microscopy. This approach may prove useful in interpreting culture and histological data in fields where cell-cell interactions play a critical role in determining cell fate, e.g., cancer, developmental
Single-cell sequencing in stem cell biology.

PubMed

Wen, Lu; Tang, Fuchou

2016-04-15

Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.
Automated Cell-Cutting for Cell Cloning

NASA Astrophysics Data System (ADS)

Ichikawa, Akihiko; Tanikawa, Tamio; Matsukawa, Kazutsugu; Takahashi, Seiya; Ohba, Kohtaro

We develop an automated cell-cutting technique for cell cloning. Animal cells softened by the cytochalasin treatment are injected into a microfluidic chip. The microfluidic chip contains two orthogonal channels: one microchannel is wide, used to transport cells, and generates the cutting flow; the other is thin and used for aspiration, fixing, and stretching of the cell. The injected cell is aspirated and stretched in the thin microchannel. Simultaneously, the volumes of the cell before and after aspiration are calculated; the volumes are used to calculate the fluid flow required to aspirate half the volume of the cell into the thin microchannel. Finally, we apply a high-speed flow in the orthogonal microchannel to bisect the cell. This paper reports the cutting process, the cutting system, and the results of the experiment.
Mir-30d suppresses cell proliferation of colon cancer cells by inhibiting cell autophagy and promoting cell apoptosis.

PubMed

Zhang, Rui; Xu, Jian; Zhao, Jian; Bai, Jinghui

2017-06-01

MiR-30 family plays an important role in the tumorigenesis of human cancers. The aim of the study is to investigate the role of miR-30d in human colon cancer cell lines and explore the molecular mechanism in the proliferation of colon cancer cells. The expression of miR-30d was determined by real-time polymerase chain reaction assay in colon cancer cell lines (HCT15, HCT116, HT-29, DLD-1, and SW480) and the results demonstrated that miR-30d level was significantly decreased in human colon cancer cell lines, compared with normal colon epithelial cell line. Transfection with miR-30d mimics inhibited cell proliferation, and transfection with miR-30d inhibitors significantly promoted cell viability of colon cancer cells. Furthermore, TargetScan analysis predicted that miR-30d interacted with messenger RNA on its 3' untranslated region of ATG5, phosphoinositide 3-kinase, and Beclin1 to negatively regulate cell autophagy in colon cancer cells. Moreover, transfection with miR-30d induced cell arrest at G2/M phase of HT-29 cells. Overexpression of miR-30d mimics inhibited cell viability probably due to the inhibition of cell autophagy and promotion of cell apoptosis. Thus, MiR-30d inhibited cell autophagy by directly targeting messenger RNA of ATG5, phosphoinositide 3-kinase, and Beclin1 and promoted cell apoptosis of human colon cancer cells. It is helpful to clarify the function of miR-30d in tumorigenesis of human cancers.
Cell volume change through water efflux impacts cell stiffness and stem cell fate

PubMed Central

Pegoraro, Adrian F.; Mao, Angelo; Zhou, Enhua H.; Arany, Praveen R.; Han, Yulong; Burnette, Dylan T.; Jensen, Mikkel H.; Kasza, Karen E.; Moore, Jeffrey R.; Mackintosh, Frederick C.; Fredberg, Jeffrey J.; Mooney, David J.; Lippincott-Schwartz, Jennifer; Weitz, David A.

2017-01-01

Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology. PMID:28973866
Femtosecond laser-induced cell-cell surgical attachment.

PubMed

Katchinskiy, Nir; Godbout, Roseline; Goez, Helly R; Elezzabi, Abdulhakem Y

2014-04-01

Laser-induced cell-cell surgical attachment using femtosecond laser pulses is reported. We have demonstrated the ability to attach single cells using sub-10 femtosecond laser pulses, with 800 nm central wavelength delivered from a Ti:Sapphire laser. To check that the cells did not go through a cell-fusion process, a fluorescent dye Calcein AM was used to verify that the fluorescent dye did not migrate from a dyed cell to a non-dyed cell. The mechanical integrity of the attached joint was assessed using an optical tweezer. Attachment of cells was performed without the induction of cell-cell fusion, with attachment efficiency of 95%, and while preserving the cells' viability. Cell-cell attachment was achieved by delivery of one to two trains of femtosecond laser pulses lasting 15 ms each. Laser-induced ionization process led to an ultrafast reversible destabilization of the phospholipid layer of the cellular membrane. The inner cell membrane remained intact during the attachment procedure, and isolation of the cells' cytoplasm from the surrounding medium was obtained. A strong physical attachment between the cells was obtained due to the bonding of the membranes' ionized phospholipid molecules and the formation of a joint cellular membrane at the connection point. The cellular attachment technique, femtosecond laser-induced cell-cell surgical attachment, can potentially provide a platform for the creation of engineered tissue and cell cultures. © 2014 Wiley Periodicals, Inc.
Induction of differentiation of human embryonic stem cells into functional hair-cell-like cells in the absence of stromal cells.

PubMed

Ding, Jie; Tang, Zihua; Chen, Jiarong; Shi, Haosong; Chen, Jianling; Wang, Cuicui; Zhang, Cui; Li, Liang; Chen, Ping; Wang, Jinfu

2016-12-01

Sensorineural hearing loss and vestibular dysfunction have become the most common forms of sensory defects. Stem cell-based therapeutic strategies for curing hearing loss are being developed. Several attempts to develop hair cells by using chicken utricle stromal cells as feeder cells have resulted in phenotypic conversion of stem cells into inner ear hair-cell-like cells. Here, we induced the differentiation of human embryonic stem cells (hESCs) into otic epithelial progenitors (OEPs), and further induced the differentiation of OEPs into hair-cell-like cells using different substrates. Our results showed that OEPs cultured on the chicken utricle stromal cells with the induction medium could differentiate into hair-cell-like cells with stereociliary bundles. Co-culture with stromal cells, however, may be problematic for subsequent examination of the induced hair-cell-like cells. In order to avoid the interference from stromal cells, we cultured OEPs on laminin with different induction media and examined the effects of the induction medium on the differentiation potentials of OEPs into hair-cell-like cells. The results revealed that the culture of OEPs on laminin with the conditioned medium from chicken utricle stromal cells supplemented with EGF and all-trans retinoic acid (RA) could promote the organization of cells into epithelial clusters displaying hair-cell-like cells with stereociliary bundles. These cells also displayed the expected electrophysiological properties. Copyright © 2015 Elsevier Ltd. All rights reserved.
CellFinder: a cell data repository

PubMed Central

Stachelscheid, Harald; Seltmann, Stefanie; Lekschas, Fritz; Fontaine, Jean-Fred; Mah, Nancy; Neves, Mariana; Andrade-Navarro, Miguel A.; Leser, Ulf; Kurtz, Andreas

2014-01-01

CellFinder (http://www.cellfinder.org) is a comprehensive one-stop resource for molecular data characterizing mammalian cells in different tissues and in different development stages. It is built from carefully selected data sets stemming from other curated databases and the biomedical literature. To date, CellFinder describes 3394 cell types and 50 951 cell lines. The database currently contains 3055 microscopic and anatomical images, 205 whole-genome expression profiles of 194 cell/tissue types from RNA-seq and microarrays and 553 905 protein expressions for 535 cells/tissues. Text mining of a corpus of >2000 publications followed by manual curation confirmed expression information on ∼900 proteins and genes. CellFinder’s data model is capable to seamlessly represent entities from single cells to the organ level, to incorporate mappings between homologous entities in different species and to describe processes of cell development and differentiation. Its ontological backbone currently consists of 204 741 ontology terms incorporated from 10 different ontologies unified under the novel CELDA ontology. CellFinder’s web portal allows searching, browsing and comparing the stored data, interactive construction of developmental trees and navigating the partonomic hierarchy of cells and tissues through a unique body browser designed for life scientists and clinicians. PMID:24304896
Cell culture purity issues and DFAT cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Shengjuan; Department of Animal Sciences, Washington State University, Pullman, WA 99164; Bergen, Werner G.

2013-04-12

Highlights: •DFAT cells are progeny cells derived from dedifferentiated mature adipocytes. •Common problems in this research is potential cell contamination of initial cultures. •The initial cell culture purity is crucial in DFAT cell research field. -- Abstract: Dedifferentiation of mature adipocytes, in vitro, has been pursued/documented for over forty years. The subsequent progeny cells are named dedifferentiated adipocyte-derived progeny cells (DFAT cells). DFAT cells are proliferative and likely to possess mutilineage potential. As a consequence, DFAT cells and their progeny/daughter cells may be useful as a potential tool for various aspects of tissue engineering and as potential vectors for themore » alleviation of several disease states. Publications in this area have been increasing annually, but the purity of the initial culture of mature adipocytes has seldom been documented. Consequently, it is not always clear whether DFAT cells are derived from dedifferentiated mature (lipid filled) adipocytes or from contaminating cells that reside in an impure culture.« less
Low Doses of Curcuma longa Modulates Cell Migration and Cell-Cell Adhesion.

PubMed

de Campos, Paloma Santos; Matte, Bibiana Franzen; Diel, Leonardo Francisco; Jesus, Luciano Henrique; Bernardi, Lisiane; Alves, Alessandro Menna; Rados, Pantelis Varvaki; Lamers, Marcelo Lazzaron

2017-09-01

Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 μM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 μM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 μM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells.

PubMed

Wang, Ran; Chen, Shuxun; Li, Changxian; Ng, Kevin Tak Pan; Kong, Chi-wing; Cheng, Jinping; Cheng, Shuk Han; Li, Ronald A; Lo, Chung Mau; Man, Kwan; Sun, Dong

2016-02-04

Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. We employed laser-induced single-cell fusion technique to fuse the hepatocellular carcinoma cells and human embryonic stem cells (hESC). Real-time RT-PCR, flow cytometry and in vivo tumorigenicity assay were adopted to identify the gene expression difference. We successfully produced a fused cell line that coalesces the gene expression information of hepatocellular carcinoma cells and stem cells. Experimental results showed that the fused cells expressed cancer and stemness markers as well as exhibited increased resistance to drug treatment and enhanced tumorigenesis. Fusion with stem cells transforms liver cancer cells into tumor initiating-like cells. Results indicate that fusion between cancer cell and stem cell may generate tumor initiating-like cells.
Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma.

PubMed

Nakanishi, Hiromi; Miyata, Yasuyoshi; Mochizuki, Yasushi; Yasuda, Takuji; Nakamura, Yuichiro; Araki, Kyohei; Sagara, Yuji; Matsuo, Tomohiro; Ohba, Kojiro; Sakai, Hideki

2018-05-19

The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index (PI), apoptotic index (AI), and microvessel density (MVD) were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multi-variate analyses (hazard ratio=1.41, 95% confidential interval=1.03-1.93, P=.031), and was significantly correlated with PI, AI, and MVD (r=.47; P <. 001, r=-.31, P<.001, and r=.40, P<.001, respectively). In conclusion, CD57+ cell, CD68+ cell, and mast cell played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis. Copyright © 2018. Published by Elsevier Inc.
The Cube and the Poppy Flower: Participatory Approaches for Designing Technology-Enhanced Learning Spaces

ERIC Educational Resources Information Center

Casanova, Diogo; Mitchell, Paul

2017-01-01

This paper presents an alternative method for learning space design that is driven by user input. An exploratory study was undertaken at an English university with the aim of redesigning technology-enhanced learning spaces. Two provocative concepts were presented through participatory design workshops during which students and teachers reflected…

Fuel cell-fuel cell hybrid system

DOEpatents

Geisbrecht, Rodney A.; Williams, Mark C.

2003-09-23

A device for converting chemical energy to electricity is provided, the device comprising a high temperature fuel cell with the ability for partially oxidizing and completely reforming fuel, and a low temperature fuel cell juxtaposed to said high temperature fuel cell so as to utilize remaining reformed fuel from the high temperature fuel cell. Also provided is a method for producing electricity comprising directing fuel to a first fuel cell, completely oxidizing a first portion of the fuel and partially oxidizing a second portion of the fuel, directing the second fuel portion to a second fuel cell, allowing the first fuel cell to utilize the first portion of the fuel to produce electricity; and allowing the second fuel cell to utilize the second portion of the fuel to produce electricity.
MARCKS-related protein regulates cytoskeletal organization at cell-cell and cell-substrate contacts in epithelial cells.

PubMed

Van Itallie, Christina M; Tietgens, Amber Jean; Aponte, Angel; Gucek, Marjan; Cartagena-Rivera, Alexander X; Chadwick, Richard S; Anderson, James M

2018-02-02

Treatment of epithelial cells with interferon-γ and TNF-α (IFN/TNF) results in increased paracellular permeability. To identify relevant proteins mediating barrier disruption, we performed proximity-dependent biotinylation (BioID) of occludin and found that tagging of MARCKS-related protein (MRP; also known as MARCKSL1) increased ∼20-fold following IFN/TNF administration. GFP-MRP was focused at the lateral cell membrane and its overexpression potentiated the physiological response of the tight junction barrier to cytokines. However, deletion of MRP did not abrogate the cytokine responses, suggesting that MRP is not required in the occludin-dependent IFN/TNF response. Instead, our results reveal a key role for MRP in epithelial cells in control of multiple actin-based structures, likely by regulation of integrin signaling. Changes in focal adhesion organization and basal actin stress fibers in MRP-knockout (KO) cells were reminiscent of those seen in FAK-KO cells. In addition, we found alterations in cell-cell interactions in MRP-KO cells associated with increased junctional tension, suggesting that MRP may play a role in focal adhesion-adherens junction cross talk. Together, our results are consistent with a key role for MRP in cytoskeletal organization of cell contacts in epithelial cells. © 2018. Published by The Company of Biologists Ltd.
Dissecting engineered cell types and enhancing cell fate conversion via CellNet

PubMed Central

Morris, Samantha A.; Cahan, Patrick; Li, Hu; Zhao, Anna M.; San Roman, Adrianna K.; Shivdasani, Ramesh A.; Collins, James J.; Daley, George Q.

2014-01-01

SUMMARY Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells. PMID:25126792
cgCorrect: a method to correct for confounding cell-cell variation due to cell growth in single-cell transcriptomics

NASA Astrophysics Data System (ADS)

Blasi, Thomas; Buettner, Florian; Strasser, Michael K.; Marr, Carsten; Theis, Fabian J.

2017-06-01

Accessing gene expression at a single-cell level has unraveled often large heterogeneity among seemingly homogeneous cells, which remains obscured when using traditional population-based approaches. The computational analysis of single-cell transcriptomics data, however, still imposes unresolved challenges with respect to normalization, visualization and modeling the data. One such issue is differences in cell size, which introduce additional variability into the data and for which appropriate normalization techniques are needed. Otherwise, these differences in cell size may obscure genuine heterogeneities among cell populations and lead to overdispersed steady-state distributions of mRNA transcript numbers. We present cgCorrect, a statistical framework to correct for differences in cell size that are due to cell growth in single-cell transcriptomics data. We derive the probability for the cell-growth-corrected mRNA transcript number given the measured, cell size-dependent mRNA transcript number, based on the assumption that the average number of transcripts in a cell increases proportionally to the cell’s volume during the cell cycle. cgCorrect can be used for both data normalization and to analyze the steady-state distributions used to infer the gene expression mechanism. We demonstrate its applicability on both simulated data and single-cell quantitative real-time polymerase chain reaction (PCR) data from mouse blood stem and progenitor cells (and to quantitative single-cell RNA-sequencing data obtained from mouse embryonic stem cells). We show that correcting for differences in cell size affects the interpretation of the data obtained by typically performed computational analysis.
Prevalence of anxiety and depression symptoms and their relationship with other coronary artery disease risk factors: A population-based study on 5900 residents in Southeast Iran.

PubMed

Najafipour, Hamid; Banivaheb, Ghodsiyeh; Sabahi, Abdolreza; Naderi, Nasrollah; Nasirian, Maryam; Mirzazadeh, Ali

2016-04-01

Anxiety and depression are reported as the most prevalent psychiatric disorders worldwide. Here, we studied the prevalence of such disorders with co-morbidities of coronary artery disease (CAD) risk factors in an urban population in Iran. 5900 people were selected from 15 to 75-years-olds through single-stage cluster sampling. In addition to examining them for CAD risk factors, Beck anxiety and depression inventories were used to measure anxiety and depression symptoms. The standardized population prevalence of such disorders is reported and the predictors of having anxiety or depression were assessed using Poisson regression model. Overall 25.4% had moderate and 22.7% had severe anxiety. Severe anxiety significantly and constantly increased by age groups (p=0.01). The risk for anxiety was higher among females (Adjusted Risk Ratio, ARR 1.2), and those who were student/soldier (ARR 1.07). Those with high level of physical activity were at lower risk for anxiety (ARR 0.92). The risk of depression (any level) was higher among females (ARR 1.3), those holding high-school level of education (ARR 1.41), and those who used opium either occasionally (ARR 1.17) or frequently (ARR 1.3). Both anxiety and depression were significantly associated with two main CAD risk factors, low physical activity and opium use. We found that the majority of residents in Kerman, particularly women, are suffering from mild to server depression and anxiety symptoms. Public health interventions to increase public awareness on such symptoms, screening and delivery of prevention and treatment services are required to prevent from the growing burden of such disorders and cardiovascular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.
Clinical and laboratory findings of rhabdomyolysis in opioid overdose patients in the intensive care unit of a poisoning center in 2014 in Iran

PubMed Central

Babak, Khoshideh; Mohammad, Arefi; Mazaher, Ghorbani; Fatemeh, Taghizadeh

2017-01-01

OBJECTIVES The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis. METHODS This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test. RESULTS A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20-29 and 30-39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%). CONCLUSIONS Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment. PMID:29121712
Clinical and laboratory findings of rhabdomyolysis in opioid overdose patients in the intensive care unit of a poisoning center in 2014 in Iran.

PubMed

Babak, Khoshideh; Mohammad, Arefi; Mazaher, Ghorbani; Samaneh, Akbarpour; Fatemeh, Taghizadeh

2017-01-01

The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis. This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test. A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20-29 and 30-39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%). Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment.
[Psychophysiological regin for rehabilition of chronic polydrug users in the Center of the Le Patriarche. 446 cases (author's transl)].

PubMed

Laffont, F; Engelmajer, L; Vourc'h, G; Nahas, G

1980-01-01

From 1974 to 1979, the rehabilitation centers of the association "Le Patriarche" located in the country side of southern France, have received 446 chronic polydrugs users who has consumed at one time or an other cannabis (marihuana, hashish) (87 p. cent), LSD (66 p. cent) and other hallucinogens (35 p. cent), psychodepressants (55 p. cent), psychostimulants (amphetamines, 85 p. cent; cocaïne, 50 p. cent) and opium and its derivatives (brown sugar, 47 p. cent; opiates, 67 p. cent; heroin, 50 p. cent). The dominant addictive drug was heroin and opiates, 52 p. cent, psychodepressants (barbitutiques and benzodiazepines, 33 p. cent, psychostimulants, 15 p. cent. Males were twice as numerous as female. Average age was 21 (range 14-38). Mean duration of drug abuse was 7 years. All these drug abusers display at entrance withdrawal symptoms. These were treated successfully by a drug free, psycho-physiological regimen comprising: 1. An elimination of all psychoactive drugs, including coffee, and alcohol. Tobacco was permitted. 2. Physical therapy (bath, exercise, massage) and forced fluid diuresis. 3. A supportive psychotherapy dispensed by rehabilitated addicts who had undergone successfully a similar regimen. This non-pharmacological method of treating withdrawal symptoms associated with opium, barbiturate and amphetamine addiction, was successful, and was not associated with any major clinical symptoms threatening the vital signs. Mean duration of detoxification was 5 days for opiates, 6 days for amphetamines and 10 days for barbiturates. 78 p. cent of these subjects remained in the centers from 3 months to 2 years, partaking in physical occupational and physiological rehabilitation paograms which allowed then to adopt a drug free life style and prepared them for social reinsertion.
Innovative Tools and Technology for Analysis of Single Cells and Cell-Cell Interaction.

PubMed

Konry, Tania; Sarkar, Saheli; Sabhachandani, Pooja; Cohen, Noa

2016-07-11

Heterogeneity in single-cell responses and intercellular interactions results from complex regulation of cell-intrinsic and environmental factors. Single-cell analysis allows not only detection of individual cellular characteristics but also correlation of genetic content with phenotypic traits in the same cell. Technological advances in micro- and nanofabrication have benefited single-cell analysis by allowing precise control of the localized microenvironment, cell manipulation, and sensitive detection capabilities. Additionally, microscale techniques permit rapid, high-throughput, multiparametric screening that has become essential for -omics research. This review highlights innovative applications of microscale platforms in genetic, proteomic, and metabolic detection in single cells; cell sorting strategies; and heterotypic cell-cell interaction. We discuss key design aspects of single-cell localization and isolation in microfluidic systems, dynamic and endpoint analyses, and approaches that integrate highly multiplexed detection of various intracellular species.
Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma.

PubMed

Liu, Shunli; Gong, Zhenyu; Chen, Mingrui; Liu, Benli; Bian, Donghui; Wu, Kai

2014-11-01

Cancer stem cells (CSCs) in most human tumors are commonly identified and enriched using similar strategies for identifying normal stem cells, including flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH) activity, and CD133 positivity. Thus, development of a method for isolating a specific cancer using cancer-specific characteristic appears to be potentially important. Here, we reported extremely high Lgr5 levels in the specimen from skin squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected high Lgr5 and CD133 levels in ALDH-high or side population from these cancer cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431 cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4-OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP-positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5-negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH-low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5-positive cells can be regenerated from Lgr5-negative cells. Furthermore, the growth of tA431 cells significantly decreased upon a single dose of diphtheria toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin SCC.
Cell tracking for cell image analysis

NASA Astrophysics Data System (ADS)

Bise, Ryoma; Sato, Yoichi

2017-04-01

Cell image analysis is important for research and discovery in biology and medicine. In this paper, we present our cell tracking methods, which is capable of obtaining fine-grain cell behavior metrics. In order to address difficulties under dense culture conditions, where cell detection cannot be done reliably since cell often touch with blurry intercellular boundaries, we proposed two methods which are global data association and jointly solving cell detection and association. We also show the effectiveness of the proposed methods by applying the method to the biological researches.
Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion*

PubMed Central

Kondo, Naoyuki; Marin, Mariana; Kim, Jeong Hwa; Desai, Tanay M.; Melikyan, Gregory B.

2015-01-01

Whether HIV-1 enters cells by fusing with the plasma membrane or with endosomes is a subject of active debate. The ability of HIV-1 to mediate fusion between adjacent cells, a process referred to as “fusion-from-without” (FFWO), shows that this virus can fuse with the plasma membrane. To compare FFWO occurring at the cell surface with HIV-cell fusion through a conventional entry route, we designed an experimental approach that enabled the measurements of both processes in the same sample. The following key differences were observed. First, a very small fraction of viruses fusing with target cells participated in FFWO. Second, whereas HIV-1 fusion with adherent cells was insensitive to actin inhibitors, post-CD4/coreceptor binding steps during FFWO were abrogated. A partial dependence of HIV-cell fusion on actin remodeling was observed in CD4+ T cells, but this effect appeared to be due to the actin dependence of virus uptake. Third, deletion of the cytoplasmic tail of HIV-1 gp41 dramatically enhanced the ability of the virus to promote FFWO, while having a modest effect on virus-cell fusion. Distinct efficiencies and actin dependences of FFWO versus HIV-cell fusion are consistent with the notion that, except for a minor fraction of particles that mediate fusion between the plasma membranes of adjacent cells, HIV-1 enters through an endocytic pathway. We surmise, however, that cell-cell contacts enabling HIV-1 fusion with the plasma membrane could be favored at the sites of high density of target cells, such as lymph nodes. PMID:25589785
Hybrid cell adhesive material for instant dielectrophoretic cell trapping and long-term cell function assessment.

PubMed

Reyes, Darwin R; Hong, Jennifer S; Elliott, John T; Gaitan, Michael

2011-08-16

Dielectrophoresis (DEP) for cell manipulation has focused, for the most part, on approaches for separation/enrichment of cells of interest. Advancements in cell positioning and immobilization onto substrates for cell culture, either as single cells or as cell aggregates, has benefited from the intensified research efforts in DEP (electrokinetic) manipulation. However, there has yet to be a DEP approach that provides the conditions for cell manipulation while promoting cell function processes such as cell differentiation. Here we present the first demonstration of a system that combines DEP with a hybrid cell adhesive material (hCAM) to allow for cell entrapment and cell function, as demonstrated by cell differentiation into neuronlike cells (NLCs). The hCAM, comprised of polyelectrolytes and fibronectin, was engineered to function as an instantaneous cell adhesive surface after DEP manipulation and to support long-term cell function (cell proliferation, induction, and differentiation). Pluripotent P19 mouse embryonal carcinoma cells flowing within a microchannel were attracted to the DEP electrode surface and remained adhered onto the hCAM coating under a fluid flow field after the DEP forces were removed. Cells remained viable after DEP manipulation for up to 8 d, during which time the P19 cells were induced to differentiate into NLCs. This approach could have further applications in areas such as cell-cell communication, three-dimensional cell aggregates to create cell microenvironments, and cell cocultures.
Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

PubMed

Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

2013-03-01

Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.
Emergence of collective propulsion through cell-cell adhesion.

PubMed

Matsushita, Katsuyoshi

2018-04-01

The mechanisms driving the collective movement of cells remain poorly understood. To contribute toward resolving this mystery, a model was formulated to theoretically explore the possible functions of polarized cell-cell adhesion in collective cell migration. The model consists of an amoeba cell with polarized cell-cell adhesion, which is controlled by positive feedback with cell motion. This model cell has no persistent propulsion and therefore exhibits a simple random walk when in isolation. However, at high density, these cells acquire collective propulsion and form ordered movement. This result suggests that cell-cell adhesion has a potential function, which induces collective propulsion with persistence.
Emergence of collective propulsion through cell-cell adhesion

NASA Astrophysics Data System (ADS)

Matsushita, Katsuyoshi

2018-04-01

The mechanisms driving the collective movement of cells remain poorly understood. To contribute toward resolving this mystery, a model was formulated to theoretically explore the possible functions of polarized cell-cell adhesion in collective cell migration. The model consists of an amoeba cell with polarized cell-cell adhesion, which is controlled by positive feedback with cell motion. This model cell has no persistent propulsion and therefore exhibits a simple random walk when in isolation. However, at high density, these cells acquire collective propulsion and form ordered movement. This result suggests that cell-cell adhesion has a potential function, which induces collective propulsion with persistence.
19. Oblique, typical cell (south cells) from rear of cell; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. Oblique, typical cell (south cells) from rear of cell; view to north, 65mm lens with electronic flash illumination. - Tule Lake Project Jail, Post Mile 44.85, State Route 139, Newell, Modoc County, CA
Llgl1 Connects Cell Polarity with Cell-Cell Adhesion in Embryonic Neural Stem Cells.

PubMed

Jossin, Yves; Lee, Minhui; Klezovitch, Olga; Kon, Elif; Cossard, Alexia; Lien, Wen-Hui; Fernandez, Tania E; Cooper, Jonathan A; Vasioukhin, Valera

2017-06-05

Malformations of the cerebral cortex (MCCs) are devastating developmental disorders. We report here that mice with embryonic neural stem-cell-specific deletion of Llgl1 (Nestin-Cre/Llgl1 fl/fl ), a mammalian ortholog of the Drosophila cell polarity gene lgl, exhibit MCCs resembling severe periventricular heterotopia (PH). Immunohistochemical analyses and live cortical imaging of PH formation revealed that disruption of apical junctional complexes (AJCs) was responsible for PH in Nestin-Cre/Llgl1 fl/fl brains. While it is well known that cell polarity proteins govern the formation of AJCs, the exact mechanisms remain unclear. We show that LLGL1 directly binds to and promotes internalization of N-cadherin, and N-cadherin/LLGL1 interaction is inhibited by atypical protein kinase C-mediated phosphorylation of LLGL1, restricting the accumulation of AJCs to the basolateral-apical boundary. Disruption of the N-cadherin-LLGL1 interaction during cortical development in vivo is sufficient for PH. These findings reveal a mechanism responsible for the physical and functional connection between cell polarity and cell-cell adhesion machineries in mammalian cells. Copyright © 2017 Elsevier Inc. All rights reserved.
Addiction and technology: Plus ça change plus c'est la même (The more things change, the more they remain the same).

PubMed

Sarin, Alok; Murthy, Pratima; Jain, Sanjeev

2017-01-01

Excessive use of the internet for gambling, gaming and behavioural addiction, are a focus of contemporary interest. The authors delve into the archives to explore the connections between the growth of various forms of technology, commerce, addictive behaviours and responses of the State, in colonial India. The interplay between the growth of the telegraph network in 19th century India, and its influence on various forms of gambling, including speculation on opium prices, and the rain, as a theme of wager make interesting stories, as do the governmental responses to these. Clinical and social responses to information technology raised much the same concerns as they do now.
[Chronic pulmonary heart disease and its risk factors among a worker population in Teheran].

PubMed

Daneshpajouh, M; Bahrami, F; Chafii, A; Kavoussi, N; Pirouzmande, B

1976-01-01

Because of the high frequency of chronic cor pulmonale in workers admitted to the cardiology department of the Khazaneh Hospital in Teheran, we studied the clinical aspect and the risk factors of this disease in 66 male patients. The average age of patients was 56.1 years and they often had a long history of bronchitis isolated or associated with emphysema. The ECG analysis showed that most abnormalities were localized on the QRST wave. Tobacco and a polluted working environment were the factors most frequently met in our patients. The opium habit probably acted as a risk factor for chronic bronchopneumopathy, but further studies are necessary to ascertain the fact.

Cell Membrane Softening in Cancer Cells

NASA Astrophysics Data System (ADS)

Schmidt, Sebastian; Händel, Chris; Käs, Josef

Biomechanical properties are useful characteristics and regulators of the cell's state. Current research connects mechanical properties of the cytoskeleton to many cellular processes but does not investigate the biomechanics of the plasma membrane. We evaluated thermal fluctuations of giant plasma membrane vesicles, directly derived from the plasma membranes of primary breast and cervical cells and observed a lowered rigidity in the plasma membrane of malignant cells compared to non-malignant cells. To investigate the specific role of membrane rigidity changes, we treated two cell lines with the Acetyl-CoA carboxylase inhibitor Soraphen A. It changed the lipidome of cells and drastically increased membrane stiffness by up regulating short chained membrane lipids. These altered cells had a decreased motility in Boyden chamber assays. Our results indicate that the thermal fluctuations of the membrane, which are much smaller than the fluctuations driven by the cytoskeleton, can be modulated by the cell and have an impact on adhesion and motility.
Hybrid clone cells derived from human breast epithelial cells and human breast cancer cells exhibit properties of cancer stem/initiating cells.

PubMed

Gauck, Daria; Keil, Silvia; Niggemann, Bernd; Zänker, Kurt S; Dittmar, Thomas

2017-08-02

The biological phenomenon of cell fusion has been associated with cancer progression since it was determined that normal cell × tumor cell fusion-derived hybrid cells could exhibit novel properties, such as enhanced metastatogenic capacity or increased drug resistance, and even as a mechanism that could give rise to cancer stem/initiating cells (CS/ICs). CS/ICs have been proposed as cancer cells that exhibit stem cell properties, including the ability to (re)initiate tumor growth. Five M13HS hybrid clone cells, which originated from spontaneous cell fusion events between M13SV1-EGFP-Neo human breast epithelial cells and HS578T-Hyg human breast cancer cells, and their parental cells were analyzed for expression of stemness and EMT-related marker proteins by Western blot analysis and confocal laser scanning microscopy. The frequency of ALDH1-positive cells was determined by flow cytometry using AldeRed fluorescent dye. Concurrently, the cells' colony forming capabilities as well as the cells' abilities to form mammospheres were investigated. The migratory activity of the cells was analyzed using a 3D collagen matrix migration assay. M13HS hybrid clone cells co-expressed SOX9, SLUG, CK8 and CK14, which were differently expressed in parental cells. A variation in the ALDH1-positive putative stem cell population was observed among the five hybrids ranging from 1.44% (M13HS-7) to 13.68% (M13HS-2). In comparison to the parental cells, all five hybrid clone cells possessed increased but also unique colony formation and mammosphere formation capabilities. M13HS-4 hybrid clone cells exhibited the highest colony formation capacity and second highest mammosphere formation capacity of all hybrids, whereby the mean diameter of the mammospheres was comparable to the parental cells. In contrast, the largest mammospheres originated from the M13HS-2 hybrid clone cells, whereas these cells' mammosphere formation capacity was comparable to the parental breast cancer cells. All M13HS
Naive T-cell receptor transgenic T cells help memory B cells produce antibody

PubMed Central

Duffy, Darragh; Yang, Chun-Ping; Heath, Andrew; Garside, Paul; Bell, Eric B

2006-01-01

Injection of the same antigen following primary immunization induces a classic secondary response characterized by a large quantity of high-affinity antibody of an immunoglobulin G class produced more rapidly than in the initial response – the products of memory B cells are qualitatively distinct from that of the original naive B lymphocytes. Very little is known of the help provided by the CD4 T cells that stimulate memory B cells. Using antigen-specific T-cell receptor transgenic CD4 T cells (DO11.10) as a source of help, we found that naive transgenic T cells stimulated memory B cells almost as well (in terms of quantity and speed) as transgenic T cells that had been recently primed. There was a direct correlation between serum antibody levels and the number of naive transgenic T cells transferred. Using T cells from transgenic interleukin-2-deficient mice we showed that interleukin-2 was not required for a secondary response, although it was necessary for a primary response. The results suggested that the signals delivered by CD4 T cells and required by memory B cells for their activation were common to both antigen-primed and naive CD4 T cells. PMID:17067314
Contact inhibition of locomotion determines cell-cell and cell-substrate forces in tissues.

PubMed

Zimmermann, Juliane; Camley, Brian A; Rappel, Wouter-Jan; Levine, Herbert

2016-03-08

Cells organized in tissues exert forces on their neighbors and their environment. Those cellular forces determine tissue homeostasis as well as reorganization during embryonic development and wound healing. To understand how cellular forces are generated and how they can influence the tissue state, we develop a particle-based simulation model for adhesive cell clusters and monolayers. Cells are contractile, exert forces on their substrate and on each other, and interact through contact inhibition of locomotion (CIL), meaning that cell-cell contacts suppress force transduction to the substrate and propulsion forces align away from neighbors. Our model captures the traction force patterns of small clusters of nonmotile cells and larger sheets of motile Madin-Darby canine kidney (MDCK) cells. In agreement with observations in a spreading MDCK colony, the cell density in the center increases as cells divide and the tissue grows. A feedback between cell density, CIL, and cell-cell adhesion gives rise to a linear relationship between cell density and intercellular tensile stress and forces the tissue into a nonmotile state characterized by a broad distribution of traction forces. Our model also captures the experimentally observed tissue flow around circular obstacles, and CIL accounts for traction forces at the edge.
Distinct T helper cell dependence of memory B-cell proliferation versus plasma cell differentiation.

PubMed

Zabel, Franziska; Fettelschoss, Antonia; Vogel, Monique; Johansen, Pål; Kündig, Thomas M; Bachmann, Martin F

2017-03-01

Several memory B-cell subclasses with distinct functions have been described, of which the most effective is the class-switched (CS) memory B-cell population. We have previously shown, using virus-like particles (VLPs), that the proliferative potential of these CS memory B cells is limited and they fail to re-enter germinal centres (GCs). However, VLP-specific memory B cells quickly differentiated into secondary plasma cells (PCs) with the virtue of elevated antibody production compared with primary PCs. Whereas the induction of VLP + memory B cells was strongly dependent on T helper cells, we were wondering whether re-stimulation of VLP + memory B cells and their differentiation into secondary PCs would also require T helper cells. Global absence of T helper cells led to strongly impaired memory B cell proliferation and PC differentiation. In contrast, lack of interleukin-21 receptor-dependent follicular T helper cells or CD40 ligand signalling strongly affected proliferation of memory B cells, but differentiation into mature secondary PCs exhibiting increased antibody production was essentially normal. This contrasts with primary B-cell responses, where a strong dependence on CD40 ligand but limited importance of interleukin-21 receptor was seen. Hence, T helper cell dependence differs between primary and secondary B-cell responses as well as between memory B-cell proliferation and PC differentiation. © 2016 John Wiley & Sons Ltd.
Non-immune cells equipped with T cell receptor-like signaling for cancer cell ablation

PubMed Central

Kojima, Ryosuke; Scheller, Leo; Fussenegger, Martin

2017-01-01

The ability to engineer custom cell-contact-sensing output devices into human non-immune cells would be useful for extending the applicability of cell-based cancer therapies and avoiding risks associated with engineered immune cells. Here, we have developed a new class of synthetic T-cell receptor-like signal-transduction device that functions efficiently in human non-immune cells and triggers release of output molecules specifically upon sensing contact with a target cell. This device employs an interleukin signaling cascade, whose OFF/ON switching is controlled by biophysical segregation of a transmembrane signal-inhibitory protein from the sensor cell/target cell interface. We further showed that designer non-immune cells equipped with this device driving expression of a membrane-penetrator/prodrug-activating enzyme construct could specifically kill target cells in the presence of the prodrug, indicating its potential usefulness for target-cell-specific, cell-based enzyme-prodrug cancer therapy. Our study also contributes to advancement of synthetic biology by extending available design principles to transmit extracellular information to cells. PMID:29131143
In vitro differentiation of primordial germ cells and oocyte-like cells from stem cells.

PubMed

Costa, José J N; Souza, Glaucinete B; Soares, Maria A A; Ribeiro, Regislane P; van den Hurk, Robert; Silva, José R V

2018-02-01

Infertility is the result of failure due to an organic disorder of the reproductive organs, especially their gametes. Recently, much progress has been made on generating germ cells, including oocytes, from various types of stem cells. This review focuses on advances in female germ cell differentiation from different kinds of stem cells, with emphasis on embryonic stem cells, adult stem cells, and induced pluripotent stem cells. The advantages and disadvantages of the derivation of female germ cells from several types of stem cells are also highlighted, as well as the ability of stem cells to generate mature and functional female gametes. This review shows that stem cell therapies have opened new frontiers in medicine, especially in the reproductive area, with the possibility of regenerating fertility.
Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC-4 cells.

PubMed

Chou, Guan-Ling; Peng, Shu-Fen; Liao, Ching-Lung; Ho, Heng-Chien; Lu, Kung-Wen; Lien, Jin-Cherng; Fan, Ming-Jen; La, Kuang-Chi; Chung, Jing-Gung

2018-02-01

Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti-cancer activities. Herein, we investigated the anti-oral cancer activity of casticin on SCC-4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca 2+ production, levels of ΔΨ m and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G 2 /M phase arrest in SCC-4 cells. Casticin promoted ROS and Ca 2+ productions, decreases the levels of ΔΨ m , promoted caspase-3, -8, and -9 activities in SCC-4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC-4 cells. In conclusion, casticin decreased cell number through G 2 /M phase arrest and the induction of cell apoptosis through caspase- and mitochondria-dependent pathways in SCC-4 cells. © 2017 Wiley Periodicals, Inc.
Bestatin Inhibits Cell Growth, Cell Division, and Spore Cell Differentiation in Dictyostelium discoideum

PubMed Central

Poloz, Yekaterina; Catalano, Andrew

2012-01-01

Bestatin methyl ester (BME) is an inhibitor of Zn2+-binding aminopeptidases that inhibits cell proliferation and induces apoptosis in normal and cancer cells. We have used Dictyostelium as a model organism to study the effects of BME. Only two Zn2+-binding aminopeptidases have been identified in Dictyostelium to date, puromycin-sensitive aminopeptidase A and B (PsaA and PsaB). PSA from other organisms is known to regulate cell division and differentiation. Here we show that PsaA is differentially expressed throughout growth and development of Dictyostelium, and its expression is regulated by developmental morphogens. We present evidence that BME specifically interacts with PsaA and inhibits its aminopeptidase activity. Treatment of cells with BME inhibited the rate of cell growth and the frequency of cell division in growing cells and inhibited spore cell differentiation during late development. Overexpression of PsaA-GFP (where GFP is green fluorescent protein) also inhibited spore cell differentiation but did not affect growth. Using chimeras, we have identified that nuclear versus cytoplasmic localization of PsaA affects the choice between stalk or spore cell differentiation pathway. Cells that overexpressed PsaA-GFP (primarily nuclear) differentiated into stalk cells, while cells that overexpressed PsaAΔNLS2-GFP (cytoplasmic) differentiated into spores. In conclusion, we have identified that BME inhibits cell growth, division, and differentiation in Dictyostelium likely through inhibition of PsaA. PMID:22345351
Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells.

PubMed

Lin, Zhiguang; Chen, Bobin; Wu, Ting; Xu, Xiaoping

2018-05-23

Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity. We created a coculture system using human DLBCL cells and mouse bone marrow stromal cells. Proliferative capacity, drug resistance, clonogenicity, and tumorigenicity were compared in lymphoma cells from the coculture system and lymphoma cells cultured alone. Expression of Notch signaling associated genes was evaluated using real-time reverse transcriptase PCR and Western blot. Lymphoma cells in the coculture system differentiated into a suspended cell group and an adherent cell group. They acquired a stronger proliferative capacity and drug resistance than lymphoma cells cultured alone, and differences existed between the adherent cell and suspended cell groups. The suspended cell group acquired the most powerful clonogenic and tumorigenic potential. However, Notch3 was exclusively expressed in the adherent lymphoma cell group and the use of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, an inhibitor of Notch pathway, could abolish the emergence of highly aggressive lymphoma cells. Highly tumorigenic lymphoma cells could be generated by coculture with stromal cells, and it was dependent on Notch3 expression in the adjacent lymphoma cells through interaction with stromal cells. © 2018 S. Karger AG, Basel.
Familial Non-VHL Clear Cell Renal Cell Carcinoma

MedlinePlus

... Cell Carcinoma Request Permissions Familial Non-VHL Clear Cell Renal Cell Carcinoma Approved by the Cancer.Net Editorial Board , 12/2017 What is familial non-VHL clear cell renal cell carcinoma? Familial non-VHL clear cell ...
Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

PubMed

Kurihara, Hidetake; Sakai, Tatsuo

2017-03-01

The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.
NK Cell-derived Exosomes From NK Cells Previously Exposed to Neuroblastoma Cells Augment the Antitumor Activity of Cytokine-activated NK Cells.

PubMed

Shoae-Hassani, Alireza; Hamidieh, Amir Ali; Behfar, Maryam; Mohseni, Rashin; Mortazavi-Tabatabaei, Seyed A; Asgharzadeh, Shahab

2017-09-01

Immune cell-derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells' effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells. Moreover, we have studied the NB-derived exosomes on NK cell function. The molecular load of the characterized exosomes (by means of nanoparticle-tracking analysis, flow cytometry, scanning electron microscopy, and western blot) from NK cells exposed to the NB cell revealed their expression of natural killer cell receptors in addition to CD56, NKG2D, and KIR2DL2 receptors. These exosomes were used to treat NK cells and thereafter administered to NB tumor cells both in vitro and in vivo. Our results showed some kind of NK cells' education by the exosomes. This education from NK cells previously exposed to NB cell-derived exosomes caused efficient and greater cytotoxicity against NB tumors, but NB-derived exosomes act as tumor promoters by providing a tumor supporting niche. Hence, this method of preparing the exosomes has a dramatic effect on activation of anti-NK cells against NB cells.
Stem cells - biological update and cell therapy progress

PubMed Central

GIRLOVANU, MIHAI; SUSMAN, SERGIU; SORITAU, OLGA; RUS-CIUCA, DAN; MELINCOVICI, CARMEN; CONSTANTIN, ANNE-MARIE; MIHU, CARMEN MIHAELA

2015-01-01

In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research. The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases. Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues. This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine. PMID:26609255
Schwann cells induce cancer cell dispersion and invasion

PubMed Central

Deborde, Sylvie; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William F.; Chernichenko, Natalya; Lee, Sei-Young; Barajas, Fernando; Chen, Chun-Hao; Bakst, Richard L.; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J.

2016-01-01

Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression. PMID:26999607
Molecular Mechanisms of HTLV-1 Cell-to-Cell Transmission

PubMed Central

Gross, Christine; Thoma-Kress, Andrea K.

2016-01-01

The tumorvirus human T-cell lymphotropic virus type 1 (HTLV-1), a member of the delta-retrovirus family, is transmitted via cell-containing body fluids such as blood products, semen, and breast milk. In vivo, HTLV-1 preferentially infects CD4+ T-cells, and to a lesser extent, CD8+ T-cells, dendritic cells, and monocytes. Efficient infection of CD4+ T-cells requires cell-cell contacts while cell-free virus transmission is inefficient. Two types of cell-cell contacts have been described to be critical for HTLV-1 transmission, tight junctions and cellular conduits. Further, two non-exclusive mechanisms of virus transmission at cell-cell contacts have been proposed: (1) polarized budding of HTLV-1 into synaptic clefts; and (2) cell surface transfer of viral biofilms at virological synapses. In contrast to CD4+ T-cells, dendritic cells can be infected cell-free and, to a greater extent, via viral biofilms in vitro. Cell-to-cell transmission of HTLV-1 requires a coordinated action of steps in the virus infectious cycle with events in the cell-cell adhesion process; therefore, virus propagation from cell-to-cell depends on specific interactions between cellular and viral proteins. Here, we review the molecular mechanisms of HTLV-1 transmission with a focus on the HTLV-1-encoded proteins Tax and p8, their impact on host cell factors mediating cell-cell contacts, cytoskeletal remodeling, and thus, virus propagation. PMID:27005656
Free-zone electrophoresis of animal cells. 1: Experiments on cell-cell interactions

NASA Technical Reports Server (NTRS)

Todd, P. W.; Hjerten, S.

1985-01-01

The electrophoretically migrating zones wasa monitored. The absence of fluid flows in the direction of migration permits direct measurement of electrophoretic velocities of any material. Sedimentation is orthogonal to electrokinetic motion and the effects of particle-particle interaction on electrophoretic mobility is studied by free zone electrophoresis. Fixed erythrocytes at high concentrations, mixtures of fixed erythrocytes from different animal species, and mixtures of cultured human cells were studied in low ionic strength buffers. The electrophoretic velocity of fixed erythrocytes was not altered by increasing cell concentration or by the mixing of erythrocytes from different species. When zones containing cultured human glial cells and neuroblastoma cells are permitted to interact during electrophoresis, altered migration patterns occur. It is found that cell-cell interactions depends upon cell type.
Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells.

PubMed

Buettner, Florian; Natarajan, Kedar N; Casale, F Paolo; Proserpio, Valentina; Scialdone, Antonio; Theis, Fabian J; Teichmann, Sarah A; Marioni, John C; Stegle, Oliver

2015-02-01

Recent technical developments have enabled the transcriptomes of hundreds of cells to be assayed in an unbiased manner, opening up the possibility that new subpopulations of cells can be found. However, the effects of potential confounding factors, such as the cell cycle, on the heterogeneity of gene expression and therefore on the ability to robustly identify subpopulations remain unclear. We present and validate a computational approach that uses latent variable models to account for such hidden factors. We show that our single-cell latent variable model (scLVM) allows the identification of otherwise undetectable subpopulations of cells that correspond to different stages during the differentiation of naive T cells into T helper 2 cells. Our approach can be used not only to identify cellular subpopulations but also to tease apart different sources of gene expression heterogeneity in single-cell transcriptomes.
Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.

PubMed

Velásquez, Celestino; Amako, Yutaka; Harold, Alexis; Toptan, Tuna; Chang, Yuan; Shuda, Masahiro

2018-01-01

Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication. The N-terminal Rb binding domain remains intact. MCV-positive cell lines derived from MCC explants have been valuable tools to study the molecular mechanism of MCV-induced Merkel cell carcinogenesis. Although all cell lines have integrated MCV and express truncated LT antigens, the molecular sizes of the LT proteins differ between cell lines. The copy number of integrated viral genome also varies across cell lines, leading to significantly different levels of viral protein expression. Nevertheless, these cell lines share phenotypic similarities in cell morphology, growth characteristics, and neuroendocrine marker expression. Several low-passage MCV-positive MCC cell lines have been established since the identification of MCV. We describe a new MCV-positive MCV cell line, CVG-1, with features distinct from previously reported cell lines. CVG-1 tumor cells grow in more discohesive clusters in loose round cell suspension, and individual cells show dramatic size heterogeneity. It is the first cell line to encode an MCV sT polymorphism resulting in a unique leucine (L) to proline (P) substitution mutation at amino acid 144. CVG-1 possesses a LT truncation pattern near identical to that of MKL-1 cells differing by the last two C-terminal amino acids and also shows an LT protein expression level similar to MKL-1. Viral T antigen knockdown reveals that, like other MCV-positive MCC cell lines, CVG-1 requires T antigen expression for cell proliferation.
c-Myc-Dependent Cell Competition in Human Cancer Cells.

PubMed

Patel, Manish S; Shah, Heta S; Shrivastava, Neeta

2017-07-01

Cell Competition is an interaction between cells for existence in heterogeneous cell populations of multicellular organisms. This phenomenon is involved in initiation and progression of cancer where heterogeneous cell populations compete directly or indirectly for the survival of the fittest based on differential gene expression. In Drosophila, cells having lower dMyc expression are eliminated by cell competition through apoptosis when present in the milieu of cells having higher dMyc expression. Thus, we designed a study to develop c-Myc (human homolog) dependent in vitro cell competition model of human cancer cells. Cells with higher c-Myc were transfected with c-myc shRNA to prepare cells with lower c-Myc and then co-cultured with the same type of cells having a higher c-Myc in equal ratio. Cells with lower c-Myc showed a significant decrease in numbers when compared with higher c-Myc cells, suggesting "loser" and "winner" status of cells, respectively. During microscopy, engulfment of loser cells by winner cells was observed with higher expression of JNK in loser cells. Furthermore, elimination of loser cells was prevented significantly, when co-cultured cells were treated with the JNK (apoptosis) inhibitor. Above results indicate elimination of loser cells in the presence of winner cells by c-Myc-dependent mechanisms of cell competition in human cancer cells. This could be an important mechanism in human tumors where normal cells are eliminated by c-Myc-overexpressed tumor cells. J. Cell. Biochem. 118: 1782-1791, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.

PubMed

Kim, Hyo-Sup; Lee, Moon-Kyu

2016-05-01

Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues. To overcome this limitation, the use of pancreatic progenitor cells is gaining more attention. In particular, pancreatic exocrine cells, such as duct epithelial cells and acinar cells, are attractive candidates for β-cell regeneration because of their differentiation potential and pancreatic lineage characteristics. It has been assumed that β-cell neogenesis from pancreatic progenitor cells could occur in pancreatic ducts in the postnatal stage. Several studies have shown that insulin-producing cells can arise in the duct tissue of the adult pancreas. Acinar cells also might have the potential to differentiate into insulin-producing cells. The present review summarizes recent progress in research on the transdifferentiation of pancreatic exocrine cells into insulin-producing cells, especially duct and acinar cells.
Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

PubMed

Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

2016-01-01

Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV ) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.
Lung cells support osteosarcoma cell migration and survival.

PubMed

Yu, Shibing; Fourman, Mitchell Stephen; Mahjoub, Adel; Mandell, Jonathan Brendan; Crasto, Jared Anthony; Greco, Nicholas Giuseppe; Weiss, Kurt Richard

2017-01-25

Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined. Three human OS cell lines (SJSA-1, Saos-2, U-2) and two human lung cell lines (HULEC-5a, MRC-5) were cultured according to American Type Culture Collection recommendations. Human lung cell lines were cultured in growth medium for 72 h to create conditioned media. OS proliferation was evaluated in lung co-culture and conditioned media microenvironment, with a murine fibroblast cell line (NIH-3 T3) in fresh growth medium as controls. Migration and invasion were measured using a real-time cell analysis system. Real-time PCR was utilized to probe for Aldehyde Dehydrogenase (ALDH1) expression. Osteosarcoma cells were also transduced with a lentivirus encoding for GFP to permit morphologic analysis with fluorescence microscopy. The anti-OS efficacy of Disulfiram, an ALDH-inhibitor previously shown to inhibit OS cell proliferation and metastasis in vitro, was evaluated in each microenvironment. Lung-cell conditioned medium promoted osteosarcoma cell migration, with a significantly higher attractive effect on all three osteosarcoma cell lines compared to basic growth medium, 10% serum containing medium, and NIH-3 T3 conditioned medium (p <0.05). Lung cell conditioned medium induced cell morphologic changes, as demonstrated with GFP-labeled cells. OS cells cultured in lung cell conditioned medium had increased
T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate.

PubMed

Ise, Wataru; Fujii, Kentaro; Shiroguchi, Katsuyuki; Ito, Ayako; Kometani, Kohei; Takeda, Kiyoshi; Kawakami, Eiryo; Yamashita, Kazuo; Suzuki, Kazuhiro; Okada, Takaharu; Kurosaki, Tomohiro

2018-04-17

Higher- or lower-affinity germinal center (GC) B cells are directed either to plasma cell or GC recycling, respectively; however, how commitment to the plasma cell fate takes place is unclear. We found that a population of light zone (LZ) GC cells, Bcl6 lo CD69 hi expressing a transcription factor IRF4 and higher-affinity B cell receptors (BCRs) or Bcl6 hi CD69 hi with lower-affinity BCRs, favored the plasma cell or recycling GC cell fate, respectively. Mechanistically, CD40 acted as a dose-dependent regulator for Bcl6 lo CD69 hi cell formation. Furthermore, we found that expression of intercellular adhesion molecule 1 (ICAM-1) and signaling lymphocytic activation molecule (SLAM) in Bcl6 lo CD69 hi cells was higher than in Bcl6 hi CD69 hi cells, thereby affording more stable T follicular helper (Tfh)-GC B cell contacts. These data support a model whereby commitment to the plasma cell begins in the GC and suggest that stability of Tfh-GC B cell contacts is key for plasma cell-prone GC cell formation. Copyright © 2018. Published by Elsevier Inc.
Cell fusion in the brain: two cells forward, one cell back.

PubMed

Kemp, Kevin; Wilkins, Alastair; Scolding, Neil

2014-11-01

Adult stem cell populations, notably those which reside in the bone marrow, have been shown to contribute to several neuronal cell types in the rodent and human brain. The observation that circulating bone marrow cells can migrate into the central nervous system and fuse with, in particular, cerebellar Purkinje cells has suggested, at least in part, a potential mechanism behind this process. Experimentally, the incidence of cell fusion in the brain is enhanced with age, radiation exposure, inflammation, chemotherapeutic drugs and even selective damage to the neurons themselves. The presence of cell fusion, shown by detection of increased bi-nucleated neurons, has also been described in a variety of human central nervous system diseases, including both multiple sclerosis and Alzheimer's disease. Accumulating evidence is therefore raising new questions into the biological significance of cell fusion, with the possibility that it represents an important means of cell-mediated neuroprotection or rescue of highly complex neurons that cannot be replaced in adult life. Here, we discuss the evidence behind this phenomenon in the rodent and human brain, with a focus on the subsequent research investigating the physiological mechanisms of cell fusion underlying this process. We also highlight how these studies offer new insights into endogenous neuronal repair, opening new exciting avenues for potential therapeutic interventions against neurodegeneration and brain injury.
Optically-Induced Cell Fusion on Cell Pairing Microstructures

NASA Astrophysics Data System (ADS)

Yang, Po-Fu; Wang, Chih-Hung; Lee, Gwo-Bin

2016-02-01

Cell fusion is a critical operation for numerous biomedical applications including cell reprogramming, hybridoma formation, cancer immunotherapy, and tissue regeneration. However, unstable cell contact and random cell pairings have limited efficiency and yields when utilizing traditional methods. Furthermore, it is challenging to selectively perform cell fusion within a group of cells. This study reports a new approach called optically-induced cell fusion (OICF), which integrates cell-pairing microstructures with an optically-induced, localized electrical field. By projecting light patterns onto a photoconductive film (hydrogen-rich, amorphous silicon) coated on an indium-tin-oxide (ITO) glass while an alternating current electrical field was applied between two such ITO glass slides, “virtual” electrodes could be generated that could selectively fuse pairing cells. At 10 kHz, a 57% cell paring rate and an 87% fusion efficiency were successfully achieved at a driving voltage of 20 Vpp, suggesting that this new technology could be promising for selective cell fusion within a group of cells.
Cell size control and a cell-intrinsic maturation program in proliferating oligodendrocyte precursor cells.

PubMed

Gao, F B; Raff, M

1997-09-22

We have used clonal analysis and time-lapse video recording to study the proliferative behavior of purified oligodendrocyte precursor cells isolated from the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from precursor cells isolated from postnatal day 7 (P7) or P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the precursor cells, just like single-celled eucaryotes, have to reach a threshold size before they can divide. These and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic events occurring in G1 proposed by "transition probability" models, may explain the random variability of cell cycle times seen within clonal cell lines in culture.
Cell Size Control and a Cell-intrinsic Maturation Program in Proliferating Oligodendrocyte Precursor Cells

PubMed Central

Gao, Fen-Biao; Raff, Martin

1997-01-01

We have used clonal analysis and time-lapse video recording to study the proliferative behavior of purified oligodendrocyte precursor cells isolated from the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from precursor cells isolated from postnatal day 7 (P7) or P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the precursor cells, just like single-celled eucaryotes, have to reach a threshold size before they can divide. These and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic events occurring in G1 proposed by “transition probability” models, may explain the random variability of cell cycle times seen within clonal cell lines in culture. PMID:9298991
Pathways of cell-cell transmission of HTLV-1

PubMed Central

Pique, Claudine; Jones, Kathryn S.

2012-01-01

The deltaretroviruses human T cell lymphotropic virus type 1 (HTLV-1) and human T cell lymphotropic virus type 2 (HTLV-2) have long been believed to differ from retroviruses in other genera by their mode of transmission. While other retroviruses were thought to primarily spread by producing cell-free particles that diffuse through extracellular fluids prior to binding to and infecting target cells, HTLV-1 and HTLV-2 were believed to transmit the virus solely by cell–cell interactions. This difference in transmission was believed to reflect the fact that, relative to other retroviruses, the cell-free virions produced by HTLV-infected cells are very poorly infectious. Since HTLV-1 and HTLV-2 are primarily found in T cells in the peripheral blood, spread of these viruses was believed to occur between infected and uninfected, T cells, although little was known about the cellular and viral proteins involved in this interaction. Recent studies have revealed that the method of transmission of HTLV is not unique: other retroviruses including human immunodeficiency virus (HIV) are also transmitted from cell-to-cell, and this method is dramatically more efficient than cell-free transmission. Moreover, cell–cell transmission of HTLV-1, as well as HIV, can occur following interactions between dendritic cells and T cells, as well as between T cells. Conversely, other studies have shown that cell-free HTLV-1 is not as poorly infectious as previously thought, since it is capable of infecting certain cell types. Here we summarize the recent insights about the mechanisms of cell–cell transmission of HTLV-1 and other retroviruses. We also review in vitro and in vivo studies of infection and discuss how these finding may relate to the spread of HTLV-1 between individuals. PMID:23109932
Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells.

PubMed

Hamano, Sayuri; Tomokiyo, Atsushi; Hasegawa, Daigaku; Yoshida, Shinichiro; Sugii, Hideki; Mitarai, Hiromi; Fujino, Shoko; Wada, Naohisa; Maeda, Hidefumi

2018-01-15

The periodontal ligament (PDL) plays an important role in anchoring teeth in the bone socket. Damage to the PDL, such as after severe inflammation, can be treated with a therapeutic strategy that uses stem cells derived from PDL tissue (PDLSCs), a strategy that has received intense scrutiny over the past decade. However, there is an insufficient number of PDLSCs within the PDL for treating such damage. Therefore, we sought to induce the differentiation of induced pluripotent stem (iPS) cells into PDLSCs as an initial step toward PDL therapy. To this end, we first induced iPS cells into neural crest (NC)-like cells. We then captured the p75 neurotrophic receptor-positive cells (iPS-NC cells) and cultured them on an extracellular matrix (ECM) produced by human PDL cells (iPS-NC-PDL cells). These iPS-NC-PDL cells showed reduced expression of embryonic stem cell and NC cell markers as compared with iPS and iPS-NC cells, and enrichment of mesenchymal stem cell markers. The cells also had a higher proliferative capacity, multipotency, and elevated expression of PDL-related markers than iPS-NC cells cultured on fibronectin and laminin (iPS-NC-FL cells) or ECM produced by human skin fibroblast cells (iPS-NC-SF cells). Overall, we present a culture method to produce high number of PDLSC-like cells from iPS cells as a first step toward a strategy for PDL regeneration.
Follow-the-leader cell migration requires biased cell-cell contact and local microenvironmental signals

NASA Astrophysics Data System (ADS)

Wynn, Michelle L.; Rupp, Paul; Trainor, Paul A.; Schnell, Santiago; Kulesa, Paul M.

2013-06-01

Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent-based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell-cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns.
PC12 Cells Differentiate into Chromaffin Cell-Like Phenotype in Coculture with Adrenal Medullary Endothelial Cells

NASA Astrophysics Data System (ADS)

Mizrachi, Yaffa; Naranjo, Jose R.; Levi, Ben-Zion; Pollard, Harvey B.; Lelkes, Peter I.

1990-08-01

Previously we described specific in vitro interactions between PC12 cells, a cloned, catecholamine-secreting pheochromocytoma cell line derived from the rat adrenal medulla, and bovine adrenal medullary endothelial cells. We now demonstrate that these interactions induce the PC12 cells to acquire physical and biochemical characteristics reminiscent of chromaffin cells. Under coculture conditions involving direct cell-cell contact, the endothelial cells and the PC12 cells reduced their rates of proliferation; upon prolonged coculture PC12 cells clustered into nests of cells similar to the organization of chromaffin cells seen in vivo. Within 3 days in coculture with endothelial cells, but not with unrelated control cells, PC12 cells synthesized increased levels of [Met]enkephalin. In addition, PC12 cells, growing on confluent endothelial monolayers, failed to extend neurites in response to nerve growth factor. Neither medium conditioned by endothelial cells nor fixed endothelial cells could by themselves induce all of these different phenomena in the PC12 cells. These results suggest that under coculture conditions PC12 cells change their state of differentiation toward a chromaffin cell-like phenotype. The rapid, transient increase in the expression of the protooncogene c-fos suggests that the mechanism(s) inducing the change in the state of differentiation in PC12 cells in coculture with the endothelial cells may be distinct from that described for the differentiation of PC12 cells--e.g., by glucocorticoids. We propose that similar interactions between endothelial cells and chromaffin cell precursors may occur during embryonic development and that these interactions might be instrumental for the organ-specific differentiation of the adrenal medulla in vivo.
Single cell transcriptomic analysis of prostate cancer cells.

PubMed

Welty, Christopher J; Coleman, Ilsa; Coleman, Roger; Lakely, Bryce; Xia, Jing; Chen, Shu; Gulati, Roman; Larson, Sandy R; Lange, Paul H; Montgomery, Bruce; Nelson, Peter S; Vessella, Robert L; Morrissey, Colm

2013-02-16

The ability to interrogate circulating tumor cells (CTC) and disseminated tumor cells (DTC) is restricted by the small number detected and isolated (typically <10). To determine if a commercially available technology could provide a transcriptomic profile of a single prostate cancer (PCa) cell, we clonally selected and cultured a single passage of cell cycle synchronized C4-2B PCa cells. Ten sets of single, 5-, or 10-cells were isolated using a micromanipulator under direct visualization with an inverted microscope. Additionally, two groups of 10 individual DTC, each isolated from bone marrow of 2 patients with metastatic PCa were obtained. RNA was amplified using the WT-Ovation™ One-Direct Amplification System. The amplified material was hybridized on a 44K Whole Human Gene Expression Microarray. A high stringency threshold, a mean Alexa Fluor® 3 signal intensity above 300, was used for gene detection. Relative expression levels were validated for select genes using real-time PCR (RT-qPCR). Using this approach, 22,410, 20,423, and 17,009 probes were positive on the arrays from 10-cell pools, 5-cell pools, and single-cells, respectively. The sensitivity and specificity of gene detection on the single-cell analyses were 0.739 and 0.972 respectively when compared to 10-cell pools, and 0.814 and 0.979 respectively when compared to 5-cell pools, demonstrating a low false positive rate. Among 10,000 randomly selected pairs of genes, the Pearson correlation coefficient was 0.875 between the single-cell and 5-cell pools and 0.783 between the single-cell and 10-cell pools. As expected, abundant transcripts in the 5- and 10-cell samples were detected by RT-qPCR in the single-cell isolates, while lower abundance messages were not. Using the same stringency, 16,039 probes were positive on the patient single-cell arrays. Cluster analysis showed that all 10 DTC grouped together within each patient. A transcriptomic profile can be reliably obtained from a single cell using
Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells.

PubMed

Aarons, Cary B; Bajenova, Olga; Andrews, Charles; Heydrick, Stanley; Bushell, Kristen N; Reed, Karen L; Thomas, Peter; Becker, James M; Stucchi, Arthur F

2007-01-01

The liver is the most common site for metastasis by colorectal cancer, and numerous studies have shown a relationship between serum carcinoembryonic antigen (CEA) levels and metastasis to this site. CEA activates hepatic macrophages or Kupffer cells via binding to the CEA receptor (CEA-R), which results in the production of cytokines and the up-regulation of endothelial adhesion molecules, both of which are implicated in hepatic metastasis. Since tissue macrophages implicated in the metastatic process can often be difficult to isolate, the aim of this study was to develop an in vitro model system to study the complex mechanisms of CEA-induced macrophage activation and metastasis. Undifferentiated, human monocytic THP-1 (U-THP) cells were differentiated (D-THP) to macrophages by exposure to 200 ng/ml phorbol myristate acetate (PMA) for 18 h. Immunohistochemistry showed two CEA-R isoforms present in both U- and D-THP cells. The receptors were localized primarily to the nucleus in U-THP cells, while a significant cell-surface presence was observed following PMA-differentiation. Incubation of D-THP-1 cells with CEA resulted in a significant increase in tumor necrosis factor-alpha (TNF-alpha) release over 24 h compared to untreated D-THP-1 or U-THP controls confirming the functionality of these cell surface receptors. U-THP cells were unresponsive to CEA. Attachment of HT-29 cells to human umbilical vein endothelial cells significantly increased at 1 h after incubation with both recombinant TNF-alpha and conditioned media from CEA stimulated D-THP cells by six and eightfold, respectively. This study establishes an in vitro system utilizing a human macrophage cell line expressing functional CEA-Rs to study activation and signaling mechanisms of CEA that facilitate tumor cell attachment to activated endothelial cells. Utilization of this in vitro system may lead to a more complete understanding of the expression and function of CEA-R and facilitate the design of anti
Traction in smooth muscle cells varies with cell spreading

NASA Technical Reports Server (NTRS)

Tolic-Norrelykke, Iva Marija; Wang, Ning

2005-01-01

Changes in cell shape regulate cell growth, differentiation, and apoptosis. It has been suggested that the regulation of cell function by the cell shape is a result of the tension in the cytoskeleton and the distortion of the cell. Here we explore the association between cell-generated mechanical forces and the cell morphology. We hypothesized that the cell contractile force is associated with the degree of cell spreading, in particular with the cell length. We measured traction fields of single human airway smooth muscle cells plated on a polyacrylamide gel, in which fluorescent microbeads were embedded to serve as markers of gel deformation. The traction exerted by the cells at the cell-substrate interface was determined from the measured deformation of the gel. The traction was measured before and after treatment with the contractile agonist histamine, or the relaxing agonist isoproterenol. The relative increase in traction induced by histamine was negatively correlated with the baseline traction. On the contrary, the relative decrease in traction due to isoproterenol was independent of the baseline traction, but it was associated with cell shape: traction decreased more in elongated than in round cells. Maximum cell width, mean cell width, and projected area of the cell were the parameters most tightly coupled to both baseline and histamine-induced traction in this study. Wide and well-spread cells exerted larger traction than slim cells. These results suggest that cell contractility is controlled by cell spreading.
Pharmacologic suppression of target cell recognition by engineered T cells expressing chimeric T-cell receptors.

PubMed

Alvarez-Vallina, L; Yañez, R; Blanco, B; Gil, M; Russell, S J

2000-04-01

Adoptive therapy with autologous T cells expressing chimeric T-cell receptors (chTCRs) is of potential interest for the treatment of malignancy. To limit possible T-cell-mediated damage to normal tissues that weakly express the targeted tumor antigen (Ag), we have tested a strategy for the suppression of target cell recognition by engineered T cells. Jurkat T cells were transduced with an anti-hapten chTCR tinder the control of a tetracycline-suppressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then reacted with hapten-coated target cells at different effector to target cell ratios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreased and recognition of the hapten-coated target cells was completely suppressed. Tetracycline-mediated suppression of target cell recognition by engineered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.
Single-cell genetic analysis validates cytopathological identification of circulating cancer cells in patients with clear cell renal cell carcinoma.

PubMed

Broncy, Lucile; Njima, Basma Ben; Méjean, Arnaud; Béroud, Christophe; Romdhane, Khaled Ben; Ilie, Marius; Hofman, Veronique; Muret, Jane; Hofman, Paul; Bouhamed, Habiba Chaabouni; Paterlini-Bréchot, And Patrizia

2018-04-13

Circulating Rare Cells (CRC) are non-haematological cells circulating in blood. They include Circulating Cancer Cells (CCC) and cells with uncertain malignant features (CRC-UMF) according to cytomorphology. Clear cell renal cell carcinomas frequently bear a mutated Von Hippel-Lindau (VHL) gene. To match blind genetic analysis of CRC and tumor samples with CRC cytopathological diagnosis. 29/30 patients harboured CRC (20 harboured CCC, 29 CRC-UMF) and 25/29 patients carried VHL mutations in their tumour. 205 single CRC (64 CCC, 141 CRC-UMF) provided genetic data. 57/57 CCC and 104/125 CRC-UMF from the 25 patients with VHL-mutated tumor carried the same VHL mutation detected in the tumor. Seven CCC and 16 CRC-UMF did not carry VHL mutations but were found in patients with wild-type VHL tumor tissue. All the CCC and 83,2% (104/125) of the CRC-UMF were found to carry the same VHL mutation identified in the corresponding tumorous tissue, validating cytopathological identification of CCC in patients with clear cell renal cell carcinoma. The blood of 30 patients with clear cell renal cell carcinoma was treated by ISET ® for CRC isolation, cytopathology and single-cell VHL mutations analysis, performed blindly and compared to VHL mutations of corresponding tumor tissues and leukocytes.
Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling

PubMed Central

Narayanan, Manikandan; Martins, Andrew J.; Tsang, John S.

2016-01-01

Quantifying heterogeneity in gene expression among single cells can reveal information inaccessible to cell-population averaged measurements. However, the expression level of many genes in single cells fall below the detection limit of even the most sensitive technologies currently available. One proposed approach to overcome this challenge is to measure random pools of k cells (e.g., 10) to increase sensitivity, followed by computational “deconvolution” of cellular heterogeneity parameters (CHPs), such as the biological variance of single-cell expression levels. Existing approaches infer CHPs using either single-cell or k-cell data alone, and typically within a single population of cells. However, integrating both single- and k-cell data may reap additional benefits, and quantifying differences in CHPs across cell populations or conditions could reveal novel biological information. Here we present a Bayesian approach that can utilize single-cell, k-cell, or both simultaneously to infer CHPs within a single condition or their differences across two conditions. Using simulated as well as experimentally generated single- and k-cell data, we found situations where each data type would offer advantages, but using both together can improve precision and better reconcile CHP information contained in single- and k-cell data. We illustrate the utility of our approach by applying it to jointly generated single- and k-cell data to reveal CHP differences in several key inflammatory genes between resting and inflammatory cytokine-activated human macrophages, delineating differences in the distribution of ‘ON’ versus ‘OFF’ cells and in continuous variation of expression level among cells. Our approach thus offers a practical and robust framework to assess and compare cellular heterogeneity within and across biological conditions using modern multiplexed technologies. PMID:27438699
Mammary stem cells have myoepithelial cell properties

PubMed Central

Prater, Michael D.; Petit, Valérie; Russell, I. Alasdair; Giraddi, Rajshekhar; Shehata, Mona; Menon, Suraj; Schulte, Reiner; Kalajzic, Ivo; Rath, Nicola; Olson, Michael F.; Metzger, Daniel; Faraldo, Marisa M.; Deugnier, Marie-Ange; Glukhova, Marina A.; Stingl, John

2014-01-01

Contractile myoepithelial cells dominate the basal layer of the mammary epithelium and are considered to be differentiated cells. However, we observe that up to 54% of single basal cells can form colonies when seeded into adherent culture in the presence of agents that disrupt acin-myosin interactions, and on average, 65% of the single-cell-derived basal colonies can repopulate a mammary gland when transplanted in vivo. This indicates that a high proportion of basal myoepithelial cells can give rise to a mammary repopulating unit (MRU). We demonstrate that myoepithelial cells, flow-sorted using 2 independent myoepithelial-specific reporter strategies, have MRU capacity. Using an inducible lineage tracing approach we follow the progeny of α-smooth muscle actin-expressing myoepithelial cells and show that they function as long-lived lineage-restricted stem cells in the virgin state and during pregnancy. PMID:25173976
The usefulness of three-dimensional cell culture in induction of cancer stem cells from esophageal squamous cell carcinoma cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujiwara, Daisuke; Kato, Kazunori, E-mail: kzkatou@juntendo.ac.jp; Department of Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421

2013-05-17

Highlights: •Spheroids were created from esophageal carcinoma cells using NanoCulture® Plates. •The proportion of strongly ALDH-positive cells increased in 3-D culture. •Expression of cancer stem cell-related genes was enhanced in 3-D culture. •CA-9 expression was enhanced, suggesting hypoxia had been induced in 3-D culture. •Drug resistance was increased. 3-D culture is useful for inducing cancer stem cells. -- Abstract: In recent years, research on resistance to chemotherapy and radiotherapy in cancer treatment has come under the spotlight, and researchers have also begun investigating the relationship between resistance and cancer stem cells. Cancer stem cells are assumed to be present inmore » esophageal cancer, but experimental methods for identification and culture of these cells have not yet been established. To solve this problem, we created spheroids using a NanoCulture® Plate (NCP) for 3-dimensional (3-D) cell culture, which was designed as a means for experimentally reproducing the 3-D structures found in the body. We investigated the potential for induction of cancer stem cells from esophageal cancer cells. Using flow cytometry we analyzed the expression of surface antigen markers CD44, CD133, CD338 (ABCG2), CD318 (CDCP1), and CD326 (EpCAM), which are known cancer stem cell markers. None of these surface antigen markers showed enhanced expression in 3-D cultured cells. We then analyzed aldehyde dehydrogenase (ALDH) enzymatic activity using the ALDEFLUOR reagent, which can identify immature cells such as stem cells and precursor cells. 3-D-cultured cells were strongly positive for ALDH enzyme activity. We also analyzed the expression of the stem cell-related genes Sox-2, Nanog, Oct3/4, and Lin28 using RT-PCR. Expression of Sox-2, Nanog, and Lin28 was enhanced. Analysis of expression of the hypoxic surface antigen marker carbonic anhydrase-9 (CA-9), which is an indicator of cancer stem cell induction and maintenance, revealed that CA-9

Procrastination and Self-Efficacy Among Intravenous Drug Users on a Methadone Maintenance Program in Sari City, Iran, 2013

PubMed Central

Taghizadeh, Fatemeh; Yazdani Cherati, Jamshid

2015-01-01

Background: Self-efficacy is the belief that one has the ability to implement the behaviors needed to produce a desired effect. There has been growing interest in the role of self-efficacy as a predictor and/or mediator of treatment outcome in a number of domains. Procrastination is a self-regulatory failure, defined as the voluntary delay of an intended course of action despite expecting to be worse off for the delay. Behavioral procrastination is a self-sabotage strategy that allows people to shift blame and avoid action; the decisional procrastination strategy is to put off making a decision when dealing with conflicts or choices. Procrastination has a great role in quitting drug addiction. Objectives: The aim of this study was to determine the relationship between procrastination and self-efficacy and other factors among intravenous drug users. Patients and Methods: This cross-sectional study was conducted on 178 intravenous drug users in the behavioral disease counseling, health center in Sari city, Mazandaran province, Iran, in 2013. The samples were selected through census sampling, descriptive and inferential statistics were used to measure the properties of distribution that depicts a set of data shown as frequency distribution tables, while for the mean and standard deviation, chi-square, Fisher and Spearman-Brown coefficients were used to analyze the data. Results: The mean age of the participants was 43 years. Seventy-two percent of them were married and opium was the first drug used. The first substance used in them was 54% of opium, 33% cannabis and 5% alcohol and 79% smoking. The reason of the first drug use in 32% of the subjects was temptation and in 10% a friend’s influence. The mean age of the first drug use was 23 years, and the frequency was 2 times per day. All of them had relapse at least once. Seven percent of them currently use other materials (2% crystal, 5% alcohol and opium and crack) both in methadone treatment. Behavioral
A novel cell division factor from tobacco 2B-13 cells that induced cell division in auxin-starved tobacco BY-2 cells

NASA Astrophysics Data System (ADS)

Shimizu, Takashi; Eguchi, Kentaro; Nishida, Ikuo; Laukens, Kris; Witters, Erwin; van Onckelen, Harry; Nagata, Toshiyuki

2006-06-01

Effects of auxin as plant hormones are widespread; in fact in almost all aspects of plant growth and development auxin plays a pivotal role. Although auxin is required for propagating cell division in plant cells, its effect upon cell division is least understood. If auxin is depleted from the culture medium, cultured cells cease to divide. It has been demonstrated in this context that the addition of auxin to auxin-starved nondividing tobacco BY-2 cells induced semisynchronous cell division. On the other hand, there are some cell lines, named habituated cells, that can grow without auxin. The cause and reason for the habituated cells have not been clarified. A habituated cell line named 2B-13 is derived from the tobacco BY-2 cell line, which has been most intensively studied among plant cell lines. When we tried to find the difference between two cell lines of BY-2 and 2B-13 cells, we found that the addition of culture filtrated from the auxin-habituated 2B-13 cells induced semisynchronous cell division in auxin-starved BY-2 cells. The cell division factor (CDF) that is responsible for inducing cell division in auxin-starved BY-2 cells was purified to near-homogeneity by sequential passage through a hydroxyapatite column, a ConA Sepharose column and a Sephadex gel filtration column. The resulting purified fraction appeared as a single band of high molecular weight on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels by silver staining and was able to induce cell division in auxin-starved BY-2 cells. Identification of the protein by MALD-TOF-MS/MS revealed that it is structurally related to P-glycoprotein from Gossypioides kirkii, which belongs to ATP-binding cassette (ABC)-transporters. The significance of CDF as a possible ABC-transporter is discussed in relationship to auxin-autotrophic growth and auxin-signaling pathway.
Cell damage evaluation of mammalian cells in cell manipulation by amplified femtosecond ytterbium laser

NASA Astrophysics Data System (ADS)

Hong, Z.-Y.; Iino, T.; Hagihara, H.; Maeno, T.; Okano, K.; Yasukuni, R.; Hosokawa, Y.

2018-03-01

A micrometer-scale explosion with cavitation bubble generation is induced by focusing a femtosecond laser in an aqueous solution. We have proposed to apply the explosion as an impulsive force to manipulate mammalian cells especially in microfluidic chip. Herein, we employed an amplified femtosecond ytterbium laser as an excitation source for the explosion and evaluated cell damage in the manipulation process to clarify the application potential. The damage of C2C12 myoblast cell prepared as a representative mammalian cell was investigated as a function of distance between cell and laser focal point. Although the cell received strong damage on the direct laser irradiation condition, the damage sharply decreased with increasing distance. Since the threshold distance, above which the cell had no damage, was consistent with radius of the cavitation bubble, impact of the cavitation bubble would be a critical factor for the cell damage. The damage had strong nonlinearity in the pulse energy dependence. On the other hand, cell position shift by the impact of the cavitation bubble was almost proportional to the pulse energy. In balance between the cell viability and the cell position shift, we elucidated controllability of the cell manipulation in microfluidic chip.
Exclusion from spheroid formation identifies loss of essential cell-cell adhesion molecules in colon cancer cells.

PubMed

Stadler, Mira; Scherzer, Martin; Walter, Stefanie; Holzner, Silvio; Pudelko, Karoline; Riedl, Angelika; Unger, Christine; Kramer, Nina; Weil, Beatrix; Neesen, Jürgen; Hengstschläger, Markus; Dolznig, Helmut

2018-01-18

Many cell lines derived from solid cancers can form spheroids, which recapitulate tumor cell clusters and are more representative of the in vivo situation than 2D cultures. During spheroid formation, a small proportion of a variety of different colon cancer cell lines did not integrate into the sphere and lost cell-cell adhesion properties. An enrichment protocol was developed to augment the proportion of these cells to 100% purity. The basis for the separation of spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation. This protocol gives rise to sub-populations of colon cancer cells with stable loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost α-catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these molecules in the corresponding spheroid-forming cells demonstrated that loss of the respective proteins were indeed responsible for the NSF phenotypes. Loss of the spheroid forming phenotype was associated with increased migration and invasion properties in all cell lines tested. Hence, we identified critical molecules involved in spheroid formation in different cancer cell lines. We present here a simple, powerful and broadly applicable method to generate new sublines of tumor cell lines to study loss of cell-cell adhesion in cancer progression.
Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence.

PubMed

Wiley, Christopher D; Flynn, James M; Morrissey, Christapher; Lebofsky, Ronald; Shuga, Joe; Dong, Xiao; Unger, Marc A; Vijg, Jan; Melov, Simon; Campisi, Judith

2017-10-01

Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations. Individual senescent cells were surprisingly heterogeneous in their gene expression signatures. This cell-to-cell variability resulted in a loss of correlation among the expression of several senescence-associated genes. Many genes encoding senescence-associated secretory phenotype (SASP) factors, a major contributor to the effects of senescent cells in vivo, showed marked variability with a subset of highly induced genes accounting for the increases observed at the population level. Inflammatory genes in clustered genomic loci showed a greater correlation with senescence compared to nonclustered loci, suggesting that these genes are coregulated by genomic location. Together, these data offer new insights into how genes are regulated in senescent cells and suggest that single markers are inadequate to identify senescent cells in vivo. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

PubMed

Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

2016-01-01

Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.
Cell-substrate impedance fluctuations of single amoeboid cells encode cell-shape and adhesion dynamics

NASA Astrophysics Data System (ADS)

Leonhardt, Helmar; Gerhardt, Matthias; Höppner, Nadine; Krüger, Kirsten; Tarantola, Marco; Beta, Carsten

2016-01-01

We show systematic electrical impedance measurements of single motile cells on microelectrodes. Wild-type cells and mutant strains were studied that differ in their cell-substrate adhesion strength. We recorded the projected cell area by time-lapse microscopy and observed irregular oscillations of the cell shape. These oscillations were correlated with long-term variations in the impedance signal. Superposed to these long-term trends, we observed fluctuations in the impedance signal. Their magnitude clearly correlated with the adhesion strength, suggesting that strongly adherent cells display more dynamic cell-substrate interactions.
B cells as accessory cells in a Con A response of a T cell clone.

PubMed

Takeuchi, M; Kakiuchi, T; Taira, S; Nariuchi, H

1987-12-01

Accessory cell (AC) function of B cells was examined in Con A response of a cloned T cell line, 22-9D, which is Thy 1+,L3T4+,Lyt2-,H-2KbDb+ and I-Ab-.22-9D cells produced IL 2 in the presence of Con A without participation of AC. For the initiation of a proliferative response to Con A, the addition of spleen cells or spleen adherent cells was required. B cells as AC were unable to induce the proliferative response. In the presence of culture supernatant of spleen cells stimulated with Con A (CAS), 22-9D cells showed proliferative response to Con A with B cell AC. The response was inhibited by a relevant monoclonal anti-I-A antibody. Although irradiated spleen cells as AC induced IL 2 receptor expression of 22-9D cells in the presence of Con A, B cells were shown to require the addition of unknown factor(s) in CAS, which was suggested to be different from IL 1, IL 2, IL 3, or IFN-gamma, for the induction of the receptor expression on 22-9D cells.
Block-Cell-Printing for live single-cell printing

PubMed Central

Zhang, Kai; Chou, Chao-Kai; Xia, Xiaofeng; Hung, Mien-Chie; Qin, Lidong

2014-01-01

A unique live-cell printing technique, termed “Block-Cell-Printing” (BloC-Printing), allows for convenient, precise, multiplexed, and high-throughput printing of functional single-cell arrays. Adapted from woodblock printing techniques, the approach employs microfluidic arrays of hook-shaped traps to hold cells at designated positions and directly transfer the anchored cells onto various substrates. BloC-Printing has a minimum turnaround time of 0.5 h, a maximum resolution of 5 µm, close to 100% cell viability, the ability to handle multiple cell types, and efficiently construct protrusion-connected single-cell arrays. The approach enables the large-scale formation of heterotypic cell pairs with controlled morphology and allows for material transport through gap junction intercellular communication. When six types of breast cancer cells are allowed to extend membrane protrusions in the BloC-Printing device for 3 h, multiple biophysical characteristics of cells—including the protrusion percentage, extension rate, and cell length—are easily quantified and found to correlate well with their migration levels. In light of this discovery, BloC-Printing may serve as a rapid and high-throughput cell protrusion characterization tool to measure the invasion and migration capability of cancer cells. Furthermore, primary neurons are also compatible with BloC-Printing. PMID:24516129
Detecting T-cell reactivity to whole cell vaccines

PubMed Central

Brusic, Ana; Hainz, Ursula; Wadleigh, Martha; Neuberg, Donna; Su, Mei; Canning, Christine M.; DeAngelo, Daniel J.; Stone, Richard M.; Lee, Jeng-Shin; Mulligan, Richard C.; Ritz, Jerome; Dranoff, Glenn; Sasada, Tetsuro; Wu, Catherine J.

2012-01-01

BCR-ABL+ K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8+ T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown. PMID:23170257
Comparative Gene Expression Profiling of Primary and Metastatic Renal Cell Carcinoma Stem Cell-Like Cancer Cells

PubMed Central

Czarnecka, Anna M.; Lewicki, Sławomir; Helbrecht, Igor; Brodaczewska, Klaudia; Koch, Irena; Zdanowski, Robert; Król, Magdalena; Szczylik, Cezary

2016-01-01

Background Recent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells—stem cell-like cancer cells (SCLCCs)—which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells. The main goal of the project was to describe the gene-expression profile of stem cell-like cancer cells of primary tumor and metastatic origin. Materials and Methods Real-time PCR analysis of stemness genes (Oct-4, Nanog and Ncam) and soft agar colony formation assay were conducted to check the stemness properties of renal cell carcinoma (RCC) cell lines. FACS analysis of CD105+ and CD133+ cells was performed on RCC cells. Isolated CD105+ cells were verified for expression of mesenchymal markers—CD24, CD146, CD90, CD73, CD44, CD11b, CD19, CD34, CD45, HLA-DR and alkaline phosphatase. Hanging drop assay was used to investigate CD105+ cell-cell cohesion. Analysis of free-floating 3D spheres formed by isolated CD105+ was verified, as spheres have been hypothesized to contain undifferentiated multipotent progenitor cells. Finally, CD105+ cells were sorted from primary (Caki-2) and metastatic (ACHN) renal cell cancer cell lines. Gene-expression profiling of sorted CD105+ cells was performed with Agilent’s human GE 4x44K v2 microarrays. Differentially expressed genes were further categorized into canonical pathways. Network analysis and downstream analysis were performed with Ingenuity Pathway Analysis. Results Metastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony-forming ability in comparison to primary RCC cell lines. Metastatic RCC cell lines harbor
Cardiac side population cells and Sca-1-positive cells.

PubMed

Nagai, Toshio; Matsuura, Katsuhisa; Komuro, Issei

2013-01-01

Since the resident cardiac stem/progenitor cells were discovered, their ability to maintain the architecture and functional integrity of adult heart has been broadly explored. The methods for isolation and purification of the cardiac stem cells are crucial for the precise analysis of their developmental origin and intrinsic potential as tissue stem cells. Stem cell antigen-1 (Sca-1) is one of the useful cell surface markers to purify the cardiac progenitor cells. Another purification strategy is based on the high efflux ability of the dye, which is a common feature of tissue stem cells. These dye-extruding cells have been called side population cells because they locate in the side of dye-retaining cells after fluorescent cell sorting. In this chapter, we describe the methodology for the isolation of cardiac SP cells and Sca-1 positive cells.
Cancer stem cells and cell size: A causal link?

PubMed

Li, Qiuhui; Rycaj, Kiera; Chen, Xin; Tang, Dean G

2015-12-01

The majority of normal animal cells are 10-20 μm in diameter. Many signaling mechanisms, notably PI3K/Akt/mTOR, Myc, and Hippo pathways, tightly control and coordinate cell growth, cell size, cell division, and cell number during homeostasis. These regulatory mechanisms are frequently deregulated during tumorigenesis resulting in wide variations in cell sizes and increased proliferation in cancer cells. Here, we first review the evidence that primitive stem cells in adult tissues are quiescent and generally smaller than their differentiated progeny, suggesting a correlation between small cell sizes with the stemness. Conversely, increased cell size positively correlates with differentiation phenotypes. We then discuss cancer stem cells (CSCs) and present some evidence that correlates cell sizes with CSC activity. Overall, a causal link between CSCs and cell size is relatively weak and remains to be rigorously assessed. In the future, optimizing methods for isolating cells based on size should help elucidate the connection between cancer cell size and CSC characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.
Stem Cells

MedlinePlus

Stem cells are cells with the potential to develop into many different types of cells in the body. They serve as a repair ... body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...
Microfluidic devices for modeling cell-cell and particle-cell interactions in the microvasculature

PubMed Central

Prabhakarpandian, Balabhaskar; Shen, Ming-Che; Pant, Kapil; Kiani, Mohammad F.

2011-01-01

Cell-fluid and cell-cell interactions are critical components of many physiological and pathological conditions in the microvasculature. Similarly, particle-cell interactions play an important role in targeted delivery of therapeutics to tissue. Development of in vitro fluidic devices to mimic these microcirculatory processes has been a critical step forward in our understanding of the inflammatory process, development of nano-particulate drug carriers, and developing realistic in vitro models of the microvasculature and its surrounding tissue. However, widely used parallel plate flow based devices and assays have a number of important limitations for studying the physiological conditions in vivo. In addition, these devices are resource hungry and time consuming for performing various assays. Recently developed, more realistic, microfluidic based devices have been able to overcome many of these limitations. In this review, an overview of the fluidic devices and their use in studying the effects of shear forces on cell-cell and cell-particle interactions is presented. In addition, use of mathematical models and Computational Fluid Dynamics (CFD) based models for interpreting the complex flow patterns in the microvasculature are highlighted. Finally, the potential of 3D microfluidic devices and imaging for better representing in vivo conditions under which cell-cell and cell-particle interactions take place are discussed. PMID:21763328
Efficient Generation of β-Globin-Expressing Erythroid Cells Using Stromal Cell-Derived Induced Pluripotent Stem Cells from Patients with Sickle Cell Disease.

PubMed

Uchida, Naoya; Haro-Mora, Juan J; Fujita, Atsushi; Lee, Duck-Yeon; Winkler, Thomas; Hsieh, Matthew M; Tisdale, John F

2017-03-01

Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell-derived erythroid cells predominantly produce ε- and γ-globin without β-globin production. We recently demonstrated that ES cell-derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β-globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation. MSC-derived iPS sacs yielded greater amounts of immature hematopoietic progenitors (VEGFR2 + GPA-), definitive HSPCs (CD34 + CD45+), and megakaryoerythroid progenitors (GPA + CD41a+), as compared to EP-derived iPS sacs. Erythroid differentiation from MSC-derived iPS sacs resulted in greater amounts of erythroid cells (GPA+) and higher β-globin (and βS-globin) expression, comparable to ES sac-derived cells. These data demonstrate that human MSC-derived iPS sacs allow for more efficient erythroid cell generation with higher β-globin production, likely due to heightened emergence of immature progenitors. Our findings should be important for iPS cell-derived erythroid cell generation. Stem Cells 2017;35:586-596. © 2016 AlphaMed Press.
Cell Patterning Chip for Controlling the Stem Cell Microenvironment

PubMed Central

Rosenthal, Adam; Macdonald, Alice; Voldman, Joel

2007-01-01

Cell-cell signaling is an important component of the stem cell microenvironment, affecting both differentiation and self-renewal. However, traditional cell-culture techniques do not provide precise control over cell-cell interactions, while existing cell patterning technologies are limited when used with proliferating or motile cells. To address these limitations, we created the Bio Flip Chip (BFC), a microfabricated polymer chip containing thousands of microwells, each sized to trap down to a single stem cell. We have demonstrated the functionality of the BFC by patterning a 50×50 grid of murine embryonic stem cells (mESCs), with patterning efficiencies > 75%, onto a variety of substrates – a cell-culture dish patterned with gelatin, a 3-D substrate, and even another layer of cells. We also used the BFC to pattern small groups of cells, with and without cell-cell contact, allowing incremental and independent control of contact-mediated signaling. We present quantitative evidence that cell-cell contact plays an important role in depressing mESC colony formation, and show that E-cadherin is involved in this negative regulatory pathway. Thus, by allowing exquisite control of the cellular microenvironment, we provide a technology that enables new applications in tissue engineering and regenerative medicine. PMID:17434582
In-cell infection: a novel pathway for Epstein-Barr virus infection mediated by cell-in-cell structures

PubMed Central

Ni, Chao; Chen, Yuhui; Zeng, Musheng; Pei, Rongjuan; Du, Yong; Tang, Linquan; Wang, Mengyi; Hu, Yazhuo; Zhu, Hanyu; He, Meifang; Wei, Xiawei; Wang, Shan; Ning, Xiangkai; Wang, Manna; Wang, Jufang; Ma, Li; Chen, Xinwen; Sun, Qiang; Tang, Hong; Wang, Ying; Wang, Xiaoning

2015-01-01

Epstein-Barr virus (EBV) can infect both susceptible B lymphocytes and non-susceptible epithelial cells (ECs). Viral tropism analyses have revealed two intriguing means of EBV infection, either by a receptor-mediated infection of B cells or by a cell-to-cell contact-mediated infection of non-susceptible ECs. Herein, we report a novel “in-cell infection” mechanism for EBV infection of non-susceptible ECs through the formation of cell-in-cell structures. Epithelial CNE-2 cells were invaded by EBV-infected Akata B cells to form cell-in-cell structures in vitro. Such unique cellular structures could be readily observed in the specimens of nasopharyngeal carcinoma. Importantly, the formation of cell-in-cell structures led to the autonomous activation of EBV within Akata cells and subsequent viral transmission to CNE-2 cells, as evidenced by the expression of viral genes and the presence of virion particles in CNE-2 cells. Significantly, EBV generated from in-cell infected ECs displayed altered tropism with higher infection efficacy to both B cells and ECs. In addition to CNE-2 tumor cells, cell-in-cell structure formation could also mediate EBV infection of NPEC1-Bmi1 cells, an immortalized nasopharyngeal epithelial cell line. Furthermore, efficient infection by this mechanism involved the activation of the PI3K/AKT signaling pathway. Thus, our study identified “in-cell infection” as a novel mechanism for EBV infection. Given the diversity of virus-infected cells and the prevalence of cell-in-cell structures during chronic infection, we speculate that “in-cell infection” is likely a general mechanism for EBV and other viruses to infect non-susceptible ECs. PMID:25916549
Determination of mammalian cell counts, cell size and cell health using the Moxi Z mini automated cell counter.

PubMed

Dittami, Gregory M; Sethi, Manju; Rabbitt, Richard D; Ayliffe, H Edward

2012-06-21

Particle and cell counting is used for a variety of applications including routine cell culture, hematological analysis, and industrial controls(1-5). A critical breakthrough in cell/particle counting technologies was the development of the Coulter technique by Wallace Coulter over 50 years ago. The technique involves the application of an electric field across a micron-sized aperture and hydrodynamically focusing single particles through the aperture. The resulting occlusion of the aperture by the particles yields a measurable change in electric impedance that can be directly and precisely correlated to cell size/volume. The recognition of the approach as the benchmark in cell/particle counting stems from the extraordinary precision and accuracy of its particle sizing and counts, particularly as compared to manual and imaging based technologies (accuracies on the order of 98% for Coulter counters versus 75-80% for manual and vision-based systems). This can be attributed to the fact that, unlike imaging-based approaches to cell counting, the Coulter Technique makes a true three-dimensional (3-D) measurement of cells/particles which dramatically reduces count interference from debris and clustering by calculating precise volumetric information about the cells/particles. Overall this provides a means for enumerating and sizing cells in a more accurate, less tedious, less time-consuming, and less subjective means than other counting techniques(6). Despite the prominence of the Coulter technique in cell counting, its widespread use in routine biological studies has been prohibitive due to the cost and size of traditional instruments. Although a less expensive Coulter-based instrument has been produced, it has limitations as compared to its more expensive counterparts in the correction for "coincidence events" in which two or more cells pass through the aperture and are measured simultaneously. Another limitation with existing Coulter technologies is the lack of metrics
Stripe-patterned thermo-responsive cell culture dish for cell separation without cell labeling.

PubMed

Kumashiro, Yoshikazu; Ishihara, Jun; Umemoto, Terumasa; Itoga, Kazuyoshi; Kobayashi, Jun; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

2015-02-11

A stripe-patterned thermo-responsive surface is prepared to enable cell separation without labeling. The thermo-responsive surface containing a 3 μm striped pattern exhibits various cell adhesion and detachment properties. A mixture of three cell types is separated on the patterned surface based on their distinct cell-adhesion properties, and the composition of the cells is analyzed by flow cytometry. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells via the IQGAP1-Rac1 pathway.

PubMed

Carmon, Kendra S; Gong, Xing; Yi, Jing; Wu, Ling; Thomas, Anthony; Moore, Catherine M; Masuho, Ikuo; Timson, David J; Martemyanov, Kirill A; Liu, Qingyun J

2017-09-08

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts, and is highly up-regulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro ; however, deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear. Here, we show that LGR5 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1), an effector of Rac1/CDC42 GTPases, in the regulation of actin cytoskeleton dynamics and cell-cell adhesion. Specifically, LGR5 decreased levels of IQGAP1 phosphorylation at Ser-1441/1443, leading to increased binding of Rac1 to IQGAP1 and thus higher levels of cortical F-actin and enhanced cell-cell adhesion. LGR5 ablation in colon cancer cells and crypt stem cells resulted in loss of cortical F-actin, reduced cell-cell adhesion, and disrupted localization of adhesion-associated proteins. No evidence of LGR5 coupling to any of the four major subtypes of heterotrimeric G proteins was found. These findings suggest that LGR5 primarily functions via the IQGAP1-Rac1 pathway to strengthen cell-cell adhesion in normal adult crypt stem cells and colon cancer cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

PubMed

Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

2018-02-27

Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.
Inference of cell-cell interactions from population density characteristics and cell trajectories on static and growing domains.

PubMed

Ross, Robert J H; Yates, C A; Baker, R E

2015-06-01

A key feature of cell migration is how cell movement is affected by cell-cell interactions. Furthermore, many cell migratory processes such as neural crest stem cell migration [Thomas and Erickson, 2008; McLennan et al., 2012] occur on growing domains or in the presence of a chemoattractant. Therefore, it is important to study interactions between migrating cells in the context of domain growth and directed motility. Here we compare discrete and continuum models describing the spatial and temporal evolution of a cell population for different types of cell-cell interactions on static and growing domains. We suggest that cell-cell interactions can be inferred from population density characteristics in the presence of motility bias, and these population density characteristics for different cell-cell interactions are conserved on both static and growing domains. We also study the expected displacement of a tagged cell, and show that different types of cell-cell interactions can give rise to cell trajectories with different characteristics. These characteristics are conserved in the presence of domain growth, however, they are diminished in the presence of motility bias. Our results are relevant for researchers who study the existence and role of cell-cell interactions in biological systems, so far as we suggest that different types of cell-cell interactions could be identified from cell density and trajectory data. Copyright © 2015 Elsevier Inc. All rights reserved.
Surface topography during neural stem cell differentiation regulates cell migration and cell morphology.

PubMed

Czeisler, Catherine; Short, Aaron; Nelson, Tyler; Gygli, Patrick; Ortiz, Cristina; Catacutan, Fay Patsy; Stocker, Ben; Cronin, James; Lannutti, John; Winter, Jessica; Otero, José Javier

2016-12-01

We sought to determine the contribution of scaffold topography to the migration and morphology of neural stem cells by mimicking anatomical features of scaffolds found in vivo. We mimicked two types of central nervous system scaffolds encountered by neural stem cells during development in vitro by constructing different diameter electrospun polycaprolactone (PCL) fiber mats, a substrate that we have shown to be topographically similar to brain scaffolds. We compared the effects of large fibers (made to mimic blood vessel topography) with those of small-diameter fibers (made to mimic radial glial process topography) on the migration and differentiation of neural stem cells. Neural stem cells showed differential migratory and morphological reactions with laminin in different topographical contexts. We demonstrate, for the first time, that neural stem cell biological responses to laminin are dependent on topographical context. Large-fiber topography without laminin prevented cell migration, which was partially reversed by treatment with rock inhibitor. Cell morphology complexity assayed by fractal dimension was inhibited in nocodazole- and cytochalasin-D-treated neural precursor cells in large-fiber topography, but was not changed in small-fiber topography with these inhibitors. These data indicate that cell morphology has different requirements on cytoskeletal proteins dependent on the topographical environment encountered by the cell. We propose that the physical structure of distinct scaffolds induces unique signaling cascades that regulate migration and morphology in embryonic neural precursor cells. J. Comp. Neurol. 524:3485-3502, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Single-cell-precision microplasma-induced cancer cell apoptosis.

PubMed

Tan, Xiao; Zhao, Shasha; Lei, Qian; Lu, Xinpei; He, Guangyuan; Ostrikov, Kostya

2014-01-01

The issue of single-cell control has recently attracted enormous interest. However, in spite of the presently achievable intracellular-level physiological probing through bio-photonics, nano-probe-based, and some other techniques, the issue of inducing selective, single-cell-precision apoptosis, without affecting neighbouring cells remains essentially open. Here we resolve this issue and report on the effective single-cell-precision cancer cell treatment using the reactive chemistry of the localized corona-type plasma discharge around a needle-like electrode with the spot size ∼1 µm. When the electrode is positioned with the micrometer precision against a selected cell, a focused and highly-localized micro-plasma discharge induces apoptosis in the selected individual HepG2 and HeLa cancer cells only, without affecting any surrounding cells, even in small cell clusters. This is confirmed by the real-time monitoring of the morphological and structural changes at the cellular and cell nucleus levels after the plasma exposure.
Stem cells.

PubMed

Behr, Björn; Ko, Sae Hee; Wong, Victor W; Gurtner, Geoffrey C; Longaker, Michael T

2010-10-01

Stem cells are self-renewing cells capable of differentiating into multiple cell lines and are classified according to their origin and their ability to differentiate. Enormous potential exists in use of stem cells for regenerative medicine. To produce effective stem cell-based treatments for a range of diseases, an improved understanding of stem cell biology and better control over stem cell fate are necessary. In addition, the barriers to clinical translation, such as potential oncologic properties of stem cells, need to be addressed. With renewed government support and continued refinement of current stem cell methodologies, the future of stem cell research is exciting and promises to provide novel reconstructive options for patients and surgeons limited by traditional paradigms.
Differentiation and Cell-Cell Interactions of Neural Progenitor Cells Transplanted into Intact Adult Brain.

PubMed

Sukhinich, K K; Kosykh, A V; Aleksandrova, M A

2015-11-01

We studied the behavior and cell-cell interactions of embryonic brain cell from GFP-reporter mice after their transplantation into the intact adult brain. Fragments or cell suspensions of fetal neocortical cells at different stages of development were transplanted into the neocortex and striatum of adult recipients. Even in intact brain, the processes of transplanted neurons formed extensive networks in the striatum and neocortical layers I and V-VI. Processes of transplanted cells at different stages of development attained the rostral areas of the frontal cortex and some of them reached the internal capsule. However, the cells transplanted in suspension had lower process growth potency than cells from tissue fragments. Tyrosine hydroxylase fibers penetrated from the recipient brain into grafts at both early and late stages of development. Our experiments demonstrated the formation of extensive reciprocal networks between the transplanted fetal neural cells and recipient brain neurons even in intact brain.
AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells

PubMed Central

Saia, Marco; Termanini, Alberto; Rizzi, Nicoletta; Mazza, Massimiliano; Barbieri, Elisa; Valli, Debora; Ciana, Paolo; Gruszka, Alicja M.; Alcalay, Myriam

2016-01-01

The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice. Our results suggest that AML1/ETO expression determines a more mobile and less adherent phenotype in preleukemic cells, therefore altering the interaction with the hematopoietic niche, potentially leading to the migration across the bone marrow barrier and to disease progression. PMID:27713544
Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks.

PubMed

Brandon, Mark P; Koenig, Julie; Leutgeb, Stefan

2014-03-01

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type-the place cell. We therefore suggest that parallel information processing in different classes of cells-as is typically observed at lower levels of sensory processing-continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207-219. doi: 10.1002/wcs.1272 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.
Myeloid-derived suppressor cells modulate B-cell responses.

PubMed

Lelis, Felipe J N; Jaufmann, Jennifer; Singh, Anurag; Fromm, Katja; Teschner, Annkathrin Chiara; Pöschel, Simone; Schäfer, Iris; Beer-Hammer, Sandra; Rieber, Nikolaus; Hartl, Dominik

2017-08-01

Myeloid-derived suppressor cells (MDSCs) are key regulators of adaptive immunity by suppressing T-cell functions. However, their potential action on or interaction with B cells remained poorly understood. Here we demonstrate that human polymorphonuclear MDSCs differentially modulate B-cell function by suppressing B-cell proliferation and antibody production. We further demonstrate that this MDSC-mediated effect is cell contact dependent and involves established mediators such as arginase-1, nitric oxide (NO), reactive oxygen species (ROS) as well as B-cell death. Collectively, our studies provide novel evidence that human MDSCs modulate B cells, which could have future implications for immunotherapy approaches. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Engineering spheroids potentiating cell-cell and cell-ECM interactions by self-assembly of stem cell microlayer.

PubMed

Lee, Yu Bin; Kim, Eun Mi; Byun, Hayeon; Chang, Hyung-Kwan; Jeong, Kwanghee; Aman, Zachary M; Choi, Yu Suk; Park, Jungyul; Shin, Heungsoo

2018-05-01

Numerous methods have been reported for the fabrication of 3D multi-cellular spheroids and their use in stem cell culture. Current methods typically relying on the self-assembly of trypsinized, suspended stem cells, however, show limitations with respect to cell viability, throughput, and accurate recapitulation of the natural microenvironment. In this study, we developed a new system for engineering cell spheroids by self-assembly of micro-scale monolayer of stem cells. We prepared synthetic hydrogels with the surface of chemically formed micropatterns (squares/circles with width/diameter of 200 μm) on which mesenchymal stem cells isolated from human nasal turbinate tissue (hTMSCs) were selectively attached and formed a monolayer. The hydrogel is capable of thermally controlled expansion. As the temperature was decreased from 37 to 4 °C, the cell layer detached rapidly (<10 min) and assembled to form spheroids with consistent size (∼100 μm) and high viability (>90%). Spheroidization was significantly delayed and occurred with reduced efficiency on circle patterns compared to square patterns. Multi-physics mapping supported that delamination of the micro-scale monolayer may be affected by stress concentrated at the corners of the square pattern. In contrast, stress was distributed symmetrically along the boundary of the circle pattern. In addition, treatment of the micro-scale monolayer with a ROCK inhibitor significantly retarded spheroidization, highlighting the importance of contraction mediated by actin stress fibers for the stable generation of spheroidal stem cell structures. Spheroids prepared from the assembly of monolayers showed higher expression, both on the mRNA and protein levels, of ECM proteins (fibronectin and laminin) and stemness markers (Oct4, Sox2, and Nanog) compared to spheroids prepared from low-attachment plates, in which trypsinized single cells are assembled. The hTMSC spheroids also presented enhanced expression levels of
Evodiamine Induces Cell Growth Arrest, Apoptosis and Suppresses Tumorigenesis in Human Urothelial Cell Carcinoma Cells.

PubMed

Shi, Chung-Sheng; Li, Jhy-Ming; Chin, Chih-Chien; Kuo, Yi-Hung; Lee, Ying-Ray; Huang, Yun-Ching

2017-03-01

Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities including vasodilatation, analgesia, anti-cardiovascular disease, anti-Alzheimer's disease, anti-inflammation, and anti-tumor activity. This study analyzes the anti-tumor effects of evodiamine on cellular growth, tumorigenesis, cell cycle and apoptosis induction of human urothelial cell carcinoma (UCC) cells. The present study showed that evodiamine significantly inhibited the proliferation of UCC cells in a dose- and time-dependent manner. Also, evodiamine suppressed the tumorigenesis of UCC cells in vitro. Moreover, evodiamine caused G 2 /M cell-cycle arrest and induced caspase-dependent apoptosis in UCC cells. Finally, we demonstrated that evodiamine exhibits better cytotoxic than 5-fluorouracil, a clinical chemotherapeutic drug, for UCC cells. Evodiamine induces growth inhibition, tumorigenesis suppression, cell-cycle arrest, and apoptosis induction in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC cells and is worthy for further investigation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Mesenchymal Stem Cells Derived from Human Limbal Niche Cells

PubMed Central

Li, Gui-Gang; Zhu, Ying-Ting; Xie, Hua-Tao; Chen, Szu-Yu; Tseng, Scheffer C. G.

2012-01-01

Purpose. We investigated whether human limbal niche cells generate mesenchymal stem cells. Methods. Limbal niche cells were isolated from the limbal stroma by collagenase alone or following dispase removal of the limbal epithelium (D/C), and cultured on plastic in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS), or coated or three-dimensional Matrigel in embryonic stem cell medium with leukemia inhibitory factor and basic fibroblast growth factor. Expression of cell markers, colony-forming units-fibroblast, tri-lineage differentiation, and ability of supporting limbal epithelial stem/progenitor cells were compared to limbal residual stromal cells. Results. Stromal cells expressing angiogenesis markers were found perivascularly, subjacent to limbal basal epithelial cells, and in D/C and limbal residual stromal cells. When seeded in three-dimensional Matrigel, D/C but not limbal residual stromal cells yielded spheres of angiogenesis progenitors that stabilized vascular networks. Similar to collagenase-isolated cells, D/C cells could be expanded on coated Matrigel for more than 12 passages, yielding spindle cells expressing angiogenesis and mesenchymal stem cells markers, and possessing significantly higher colony-forming units-fibroblast and more efficient tri-lineage differentiation than D/C and limbal residual stromal cells expanded on plastic in DMEM with 10% FBS, of which both lost the pericyte phenotype while limbal residual stromal cells turned into myofibroblasts. Upon reunion with limbal epithelial stem/progenitor cells to form spheres, D/C cells expanded on coated Matrigel maintained higher expression of p63α and lower expression of cytokeratin 12 than those expanded on plastic in DMEM with 10% FBS, while spheres formed with human corneal fibroblasts expressed cytokeratin 12 without p63α. Conclusions. In the limbal stroma, cells subjacent to limbal basal epithelial cells serve as niche cells, and generate progenitors with
Nanodiamond internalization in cells and the cell uptake mechanism

NASA Astrophysics Data System (ADS)

Perevedentseva, E.; Hong, S.-F.; Huang, K.-J.; Chiang, I.-T.; Lee, C.-Y.; Tseng, Y.-T.; Cheng, C.-L.

2013-08-01

Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.
Natural Killer Cell Immunotherapy Targeting Cancer Stem Cells

PubMed Central

Luna, Jesus I; Grossenbacher, Steven K.; Murphy, William J; Canter, Robert J

2017-01-01

Introduction Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with “stem-cell” like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. In this report, we review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert Opinion Unlike cytotoxic cancer treatments, NK cells are able to target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells. PMID:27960589
Pluripotent stem cells and reprogrammed cells in farm animals.

PubMed

Nowak-Imialek, Monika; Kues, Wilfried; Carnwath, Joseph W; Niemann, Heiner

2011-08-01

Pluripotent cells are unique because of their ability to differentiate into the cell lineages forming the entire organism. True pluripotent stem cells with germ line contribution have been reported for mice and rats. Human pluripotent cells share numerous features of pluripotentiality, but confirmation of their in vivo capacity for germ line contribution is impossible due to ethical and legal restrictions. Progress toward derivation of embryonic stem cells from domestic species has been made, but the derived cells were not able to produce germ line chimeras and thus are termed embryonic stem-like cells. However, domestic animals, in particular the domestic pig (Sus scrofa), are excellent large animals models, in which the clinical potential of stem cell therapies can be studied. Reprogramming technologies for somatic cells, including somatic cell nuclear transfer, cell fusion, in vitro culture in the presence of cell extracts, in vitro conversion of adult unipotent spermatogonial stem cells into germ line derived pluripotent stem cells, and transduction with reprogramming factors have been developed with the goal of obtaining pluripotent, germ line competent stem cells from domestic animals. This review summarizes the present state of the art in the derivation and maintenance of pluripotent stem cells in domestic animals.
Cell labeling with magnetic nanoparticles: Opportunity for magnetic cell imaging and cell manipulation

PubMed Central

2013-01-01

This tutorial describes a method of controlled cell labeling with citrate-coated ultra small superparamagnetic iron oxide nanoparticles. This method may provide basically all kinds of cells with sufficient magnetization to allow cell detection by high-resolution magnetic resonance imaging (MRI) and to enable potential magnetic manipulation. In order to efficiently exploit labeled cells, quantify the magnetic load and deliver or follow-up magnetic cells, we herein describe the main requirements that should be applied during the labeling procedure. Moreover we present some recommendations for cell detection and quantification by MRI and detail magnetic guiding on some real-case studies in vitro and in vivo. PMID:24564857
Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks

PubMed Central

Brandon, Mark P; Koenig, Julie; Leutgeb, Stefan

2014-01-01

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type—the place cell. We therefore suggest that parallel information processing in different classes of cells—as is typically observed at lower levels of sensory processing—continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207–219. doi: 10.1002/wcs.1272 PMID:24587849
Cell wall layers delimit cell groups derived from cell division in the foliose trebouxiophycean alga Prasiola japonica.

PubMed

Mine, Ichiro; Kinoshita, Urara; Kawashima, Shigetaka; Sekida, Satoko

2018-01-22

The cells in the foliose thallus of trebouxiophycean alga Prasiola japonica apparently develop into 2 × 2 cell groups composed of two two-celled groups, each of which is a pair of derivative cells of the latest cell division. In the present study, the structural features of cell walls of the alga P. japonica concerning the formation of the cell groups were investigated using histochemical methods. Thin cell layers stained by Calcofluor White appeared to envelope the two-celled and four-celled groups separately and, hence, separated them from neighboring cell groups, and the Calcofluor White-negative gaps between neighboring four-celled groups were specifically stained by lectins, such as soybean agglutinin, jacalin, and Vicia villosa lectin conjugated with fluorescein. These results indicated that the Calcofluor White-positive cell wall layer of parent cell that existed during two successive cell divisions structurally distinguished two-celled and four-celled groups from others in this alga. Moreover, the results suggested that the cell wall components of the Calcofluor White-negative gaps would possibly contribute to the formation of the planar thallus through lateral union of the cell groups.
HOT CELL BUILDING, TRA632, INTERIOR. CELL 3, "HEAVY" CELL. CAMERA ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

HOT CELL BUILDING, TRA-632, INTERIOR. CELL 3, "HEAVY" CELL. CAMERA FACES WEST TOWARD BUILDING EXIT. OBSERVATION WINDOW AT LEFT EDGE OF VIEW. INL NEGATIVE NO. HD46-28-4. Mike Crane, Photographer, 2/2005 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

The Emerging Cell Biology of Thyroid Stem Cells

PubMed Central

Latif, Rauf; Minsky, Noga C.; Ma, Risheng

2011-01-01

Context: Stem cells are undifferentiated cells with the property of self-renewal and give rise to highly specialized cells under appropriate local conditions. The use of stem cells in regenerative medicine holds great promise for the treatment of many diseases, including those of the thyroid gland. Evidence Acquisition: This review focuses on the progress that has been made in thyroid stem cell research including an overview of cellular and molecular events (most of which were drawn from the period 1990–2011) and discusses the remaining problems encountered in their differentiation. Evidence Synthesis: Protocols for the in vitro differentiation of embryonic stem cells, based on normal developmental processes, have generated thyroid-like cells but without full thyrocyte function. However, agents have been identified, including activin A, insulin, and IGF-I, which are able to stimulate the generation of thyroid-like cells in vitro. In addition, thyroid stem/progenitor cells have been identified within the normal thyroid gland and within thyroid cancers. Conclusions: Advances in thyroid stem cell biology are providing not only insight into thyroid development but may offer therapeutic potential in thyroid cancer and future thyroid cell replacement therapy. PMID:21778219
Myeloid-derived suppressor cells regulate T cell and B cell responses during autoimmune disease.

PubMed

Crook, Kristen R; Jin, Mengyao; Weeks, Michael F; Rampersad, Rishi R; Baldi, Robert M; Glekas, Amy S; Shen, Yajuan; Esserman, Denise A; Little, Paul; Schwartz, Todd A; Liu, Peng

2015-03-01

MDSCs are a heterogeneous group of myeloid cells that suppress T cell activity in cancer and autoimmune disease. The effect of MDSCs on B cell function is not clear. Using the CIA model of autoimmune disease, we found an increase in M-MDSCs in the periphery of WT mice with CIA compared with naïve mice. These MDSCs were absent from the periphery of CCR2(-/-) mice that developed exacerbated disease. M-MDSCs, isolated from immunized mice, inhibited autologous CD4(+) T cell proliferation. The M-MDSC-mediated suppression of T cell proliferation was NO and IFN-γ dependent but IL-17 independent. Furthermore, we demonstrated for the first time that M-MDSCs from CIA mice also inhibited autologous B cell proliferation and antibody production. The suppression of B cells by M-MDSCs was dependent on the production of NO and PGE2 and required cell-cell contact. Administration of M-MDSCs rescued CCR2(-/-) mice from the exacerbated CIA phenotype and ameliorated disease in WT mice. Furthermore, adoptive transfer of M-MDSCs reduced autoantibody production by CCR2(-/-) and WT mice. In summary, M-MDSCs inhibit T cell and B cell function in CIA and may serve as a therapeutic approach in the treatment of autoimmune arthritis. © Society for Leukocyte Biology.
The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.

PubMed

Yan, Chang; Hu, Yibing; Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

2016-12-06

Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA. Our findings show that the abundance of CEA-/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA-/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA-/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA-/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA-/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA-/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies.
Single-Cell Sequencing Technologies for Cardiac Stem Cell Studies.

PubMed

Liu, Tiantian; Wu, Hongjin; Wu, Shixiu; Wang, Charles

2017-11-01

Today with the rapid advancements in stem cell studies and the promising potential of using stem cells in clinical therapy, there is an increasing demand for in-depth comprehensive analysis on individual cell transcriptome and epigenome, as they play critical roles in a number of cell functions such as cell differentiation, growth, and reprogramming. The development of single-cell sequencing technologies has helped in revealing some exciting new perspectives in stem cells and regenerative medicine research. Among the various potential applications, single-cell analysis for cardiac stem cells (CSCs) holds tremendous promises in understanding the mechanisms of heart development and regeneration, which might light up the path toward cell therapy for cardiovascular diseases. This review briefly highlights the recent progresses in single-cell sequencing analysis technologies and their applications in CSC research.
Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells.

PubMed

Bruno, Silvia; Ledda, Bernardetta; Tenca, Claudya; Ravera, Silvia; Orengo, Anna Maria; Mazzarello, Andrea Nicola; Pesenti, Elisa; Casciaro, Salvatore; Racchi, Omar; Ghiotto, Fabio; Marini, Cecilia; Sambuceti, Gianmario; DeCensi, Andrea; Fais, Franco

2015-09-08

B-cell chronic lymphocytic leukemia (CLL) was believed to result from clonal accumulation of resting apoptosis-resistant malignant B lymphocytes. However, it became increasingly clear that CLL cells undergo, during their life, iterative cycles of re-activation and subsequent clonal expansion. Drugs interfering with CLL cell cycle entry would be greatly beneficial in the treatment of this disease. 1, 1-Dimethylbiguanide hydrochloride (metformin), the most widely prescribed oral hypoglycemic agent, inexpensive and well tolerated, has recently received increased attention for its potential antitumor activity. We wondered whether metformin has apoptotic and anti-proliferative activity on leukemic cells derived from CLL patients. Metformin was administered in vitro either to quiescent cells or during CLL cell activation stimuli, provided by classical co-culturing with CD40L-expressing fibroblasts. At doses that were totally ineffective on normal lymphocytes, metformin induced apoptosis of quiescent CLL cells and inhibition of cell cycle entry when CLL were stimulated by CD40-CD40L ligation. This cytostatic effect was accompanied by decreased expression of survival- and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. In drug combination experiments, metformin lowered the apoptotic threshold and potentiated the cytotoxic effects of classical and novel antitumor molecules. Our results indicate that, while CLL cells after stimulation are in the process of building their full survival and cycling armamentarium, the presence of metformin affects this process.
Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties

PubMed Central

Leung, Elaine Lai-Han; Fiscus, Ronald R.; Tung, James W.; Tin, Vicky Pui-Chi; Cheng, Lik Cheung; Sihoe, Alan Dart-Loon; Fink, Louis M.; Ma, Yupo; Wong, Maria Pik

2010-01-01

Background The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44− cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44− cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44− cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify
Satellite Cells and the Muscle Stem Cell Niche

PubMed Central

Yin, Hang; Price, Feodor

2013-01-01

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration. PMID:23303905
A systematic review on status of lead pollution and toxicity in Iran; Guidance for preventive measures

PubMed Central

2012-01-01

Lead is an old environmental metal which is presented everywhere and lead poisoning is an important health issue in many countries in the world including Iran. It is known as a silent environmental disease which can have life-long adverse health effects. In children, the most vulnerable population, mental development of children health effects is of the greatest influence. Low level lead exposure can significantly induce motor dysfunctions and cognitive impairment in children. The sources of lead exposure vary among countries. Occupational lead exposure is an important health issue in Iran and mine workers, employees of paint factories, workers of copying centers, drivers, and tile making factories are in higher risk of lead toxicity. Moreover lead processing industry has always been a major of concern which affects surface water, drinking waters, and ground waters, even water of Caspian Sea, Persian Gulf and rivers due to increasing the number of industries in vicinity of rivers that release their waste discharges into river or sea. In addition, lead contamination of soil and air especially in vicinity of polluted and industrialized cities is another health problem in Iran. Even foods such as rice and fishes, raw milk, and vegetables which are the most common food of Iranian population are polluted to lead in some area of Iran. Adding lead to the opium is a recently health hazard in Iran that has been observed among opium addicts. There are few studies evaluated current status of lead exposure and toxicity in the Iranian children and pregnant women which should be taken into account of authorities. We recommend to identify sources, eliminate or control sources, and monitor environmental exposures and hazards to prevent lead poisoning. PMID:23226111
[Lettuce, lactuca sp., as a medicinal plant in polish publications of the 19th century].

PubMed

Trojanowska, Anna

2005-01-01

Mentions of lettuce Lactuca sp. that have appeared since antiquity contained similar information on its curative properties, but such properties were ascribed to different species or varieties. Apart from the wild and poisonous lettuce, also garden or common lettuce were identified as having curative action, and some publications lacked information enabling the precise identification of the lettuce in question. In the 19th century, attempts were made to put some order into the knowledge of lettuce as a medicinal plant. Information contained in Polish medical studies of the 19th century on lettuce points to the poisonous species, Lactuca virosa, and the common or garden lettuce, Lactuca sativa v. Lactuca hortensis, as being used as a medicinal plant. In that period, lettuce and especially the the desiccated lactescent juice obtained from it, lactucarium, were considered to be an intoxicant, and were used as a sedative and an analgesic. The action of the substance was weaker than that of opium but free of the side-effects, and medical practice showed that in some cases lactucarium produced better curative effects than opium. To corroborate those properties of lettuce and its lactescent juice, studies were undertaken to find the substance responsible for the curative effects of the juice. However, such studies failed to produce the expected results, and the component responsible for the curative properties of letuce was not identified. Medical practice thus had to restrict itself to the uses of the desiccated lactescent juice and extracts obtained from it. The possibility of obtaining lactucarium from plants cultivated in Poland caused Polish pharmacists and physicians to take an interest in the stuff and launch their own research of lettuce and the lactescent juice obtained from it. Results of research on lettuce were published in 19th-century journals by, among others, Jan Fryderyk Wolfgang, Florian Sawiczewski and Józef Orkisz.
Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells.

PubMed

Singh, Brajesh K; Li, Ni; Mark, Anna C; Mateo, Mathieu; Cattaneo, Roberto; Sinn, Patrick L

2016-08-01

Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-μm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-μm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to-cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE. Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell-free particles. In
TOPICAL REVIEW: Stem cells engineering for cell-based therapy

NASA Astrophysics Data System (ADS)

Taupin, Philippe

2007-09-01

Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.
Henrietta Lacks, HeLa cells, and cell culture contamination.

PubMed

Lucey, Brendan P; Nelson-Rees, Walter A; Hutchins, Grover M

2009-09-01

Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line. HeLa cells were used by researchers around the world. However, 20 years after Henrietta Lacks' death, mounting evidence suggested that HeLa cells contaminated and overgrew other cell lines. Cultures, supposedly of tissues such as breast cancer or mouse, proved to be HeLa cells. We describe the history behind the development of HeLa cells, including the first published description of Ms Lacks' autopsy, and the cell culture contamination that resulted. The debate over cell culture contamination began in the 1970s and was not harmonious. Ultimately, the problem was not resolved and it continues today. Finally, we discuss the philosophical implications of the immortal HeLa cell line.
CellNet: network biology applied to stem cell engineering.

PubMed

Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

2014-08-14

Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.
CellNet: Network Biology Applied to Stem Cell Engineering

PubMed Central

Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

2014-01-01

SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793
Pro-Inflammatory Activated Kupffer Cells by Lipids Induce Hepatic NKT Cells Deficiency through Activation-Induced Cell Death

PubMed Central

Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

2013-01-01

Background Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. Aims The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Methods Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. Results High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. Conclusion High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD. PMID:24312613
When Blood Cells Bend: Understanding Sickle Cell Disease

MedlinePlus

... Subscribe April 2012 Print this issue When Blood Cells Bend Understanding Sickle Cell Disease Send us your ... Diabetes? Sound Health Wise Choices Living with Sickle Cell Disease See a sickle cell disease expert regularly. ...
Stabilization of apoptotic cells: generation of zombie cells.

PubMed

Oropesa-Ávila, M; Andrade-Talavera, Y; Garrido-Maraver, J; Cordero, M D; de la Mata, M; Cotán, D; Paz, M V; Pavón, A D; Alcocer-Gómez, E; de Lavera, I; Lema, R; Zaderenko, A P; Rodríguez-Moreno, A; Sánchez-Alcázar, J A

2014-08-14

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn(2+) (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy.
Stabilization of apoptotic cells: generation of zombie cells

PubMed Central

Oropesa-Ávila, M; Andrade-Talavera, Y; Garrido-Maraver, J; Cordero, M D; de la Mata, M; Cotán, D; Paz, M V; Pavón, A D; Alcocer-Gómez, E; de Lavera, I; Lema, R; Zaderenko, A P; Rodríguez-Moreno, A; Sánchez-Alcázar, J A

2014-01-01

Apoptosis is characterized by degradation of cell components but plasma membrane remains intact. Apoptotic microtubule network (AMN) is organized during apoptosis forming a cortical structure beneath plasma membrane that maintains plasma membrane integrity. Apoptotic cells are also characterized by high reactive oxygen species (ROS) production that can be potentially harmful for the cell. The aim of this study was to develop a method that allows stabilizing apoptotic cells for diagnostic and therapeutic applications. By using a cocktail composed of taxol (a microtubule stabilizer), Zn2+ (a caspase inhibitor) and coenzyme Q10 (a lipid antioxidant), we were able to stabilize H460 apoptotic cells in cell cultures for at least 72 h, preventing secondary necrosis. Stabilized apoptotic cells maintain many apoptotic cell characteristics such as the presence of apoptotic microtubules, plasma membrane integrity, low intracellular calcium levels and mitochondrial polarization. Apoptotic cell stabilization may open new avenues in apoptosis detection and therapy. PMID:25118929
Are cancer cells really softer than normal cells?

PubMed

Alibert, Charlotte; Goud, Bruno; Manneville, Jean-Baptiste

2017-05-01

Solid tumours are often first diagnosed by palpation, suggesting that the tumour is more rigid than its surrounding environment. Paradoxically, individual cancer cells appear to be softer than their healthy counterparts. In this review, we first list the physiological reasons indicating that cancer cells may be more deformable than normal cells. Next, we describe the biophysical tools that have been developed in recent years to characterise and model cancer cell mechanics. By reviewing the experimental studies that compared the mechanics of individual normal and cancer cells, we argue that cancer cells can indeed be considered as softer than normal cells. We then focus on the intracellular elements that could be responsible for the softening of cancer cells. Finally, we ask whether the mechanical differences between normal and cancer cells can be used as diagnostic or prognostic markers of cancer progression. © 2017 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.
T cell-B cell interactions in primary immunodeficiencies.

PubMed

Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

2012-02-01

Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

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