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  1. Article ; Online: Direct and straightforward transfer of C1 functionalized synthons to phosphorous electrophiles for accessing gem-P-containing methanes.

    Touqeer, Saad / Ielo, Laura / Miele, Margherita / Urban, Ernst / Holzer, Wolfgang / Pace, Vittorio

    Organic & biomolecular chemistry

    2021  Volume 19, Issue 11, Page(s) 2425–2429

    Abstract: ... as an effective strategy to synthesize geminal P-containing methanes. The methodology relies on the efficient ... nucleophilic substitution conducted on the P-chlorine linkage. Uniformly high yields are observed regardless ...

    Abstract The direct transfer of different α-substituted methyllithium reagents to chlorinated phosphorous electrophiles of diverse oxidation state (phosphates, phosphine oxides and phosphines) is proposed as an effective strategy to synthesize geminal P-containing methanes. The methodology relies on the efficient nucleophilic substitution conducted on the P-chlorine linkage. Uniformly high yields are observed regardless the specific nature of the carbanion employed: once established the conditions for generating the competent nucleophile (LiCH
    Language English
    Publishing date 2021-03-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/d1ob00273b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Conference proceedings: Spontan subluxierte, irisfixierte, phake Intraokularlinsen – eine Materialanalyse im Labor (P)

    Tandogan, Tamer / Khoramnia, Ramin / Choi, Chul Young / Auffarth, Gerd Uwe / Holzer, Mike P.

    2016  , Page(s) WK 4.10

    Event/congress 29. Internationaler Kongress der Deutschen Ophthalmochirurgen; Nürnberg; 2016
    Keywords Medizin, Gesundheit
    Publishing date 2016-06-03
    Publisher German Medical Science GMS Publishing House; Düsseldorf
    Document type Conference proceedings
    DOI 10.3205/16doc099
    Database German Medical Science

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  3. Article: Direct and Chemoselective Electrophilic Monofluoromethylation of Heteroatoms (O-, S-, N-, P-, Se-) with Fluoroiodomethane

    Senatore, Raffaele / Malik, Monika / Spreitzer, Markus / Holzer, Wolfgang / Pace, Vittorio

    Organic letters. 2020 Jan. 31, v. 22, no. 4

    2020  

    Abstract: The commercially available fluoroiodomethane represents a valuable and effective electrophilic source for transferring the CH2F unit to a series of heteroatom-centered nucleophiles under mild basic conditions. The excellent manipulability offered by its ... ...

    Abstract The commercially available fluoroiodomethane represents a valuable and effective electrophilic source for transferring the CH2F unit to a series of heteroatom-centered nucleophiles under mild basic conditions. The excellent manipulability offered by its liquid physical state (bp 53.4 °C) enables practical and straightforward one-step nucleophilic substitutions to retain the chiral information embodied, thus allowing it to overcome de facto the requirement for fluoromethylating agents with no immediate access. The high-yielding methodology was successfully applied to a variety of nucleophiles including a series of drugs currently in the market.
    Keywords Lewis acids ; Lewis bases ; chemical reactions ; chemical structure ; chemoselectivity ; drugs ; liquids ; markets ; organic compounds
    Language English
    Dates of publication 2020-0131
    Size p. 1345-1349.
    Publishing place American Chemical Society
    Document type Article
    ISSN 1523-7052
    DOI 10.1021/acs.orglett.9b04654
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Warum versagen Substanz P (NK1)-Rezeptorantagonisten in der Schmerztherapie?

    Herbert, M K / Holzer, P

    Der Anaesthesist

    2002  Volume 51, Issue 4, Page(s) 308–319

    Abstract: The undecapeptide substance P is expressed by primary afferent neurons where it is considered to be ... with unmyelinated fibres (C-fibres), substance P has long been thought to be a "pain transmitter". Following ... stimulation of nociceptive afferents, substance P is released in the spinal cord and substance P-mediated ...

    Title translation Why are substance P(NK1)-receptor antagonists ineffective in pain treatment?.
    Abstract The undecapeptide substance P is expressed by primary afferent neurons where it is considered to be a cotransmitter of other peptides and glutamate. Since it is predominantly found in sensory neurons with unmyelinated fibres (C-fibres), substance P has long been thought to be a "pain transmitter". Following stimulation of nociceptive afferents, substance P is released in the spinal cord and substance P-mediated transmission is primarily brought about by tachykinin NK1 receptors. To inhibit this process, a considerable number of non-peptide, highly potent, highly selective and brain penetrant NK1 receptor antagonists have been developed during the past decade. Experimental studies have proved that NK1 receptor antagonists are indeed able to blunt pain in sensitized states and thus to reverse hyperalgesia, whereas acute pain is left fairly unchanged. The hyperalgesic role of substance P has been corroborated by the sensory deficits seen in substance P and NK1 receptor knockout mice. However, the concept that NK1 receptor antagonists would represent a novel class of analgesic drugs, as suggested by the preclinical studies, has not been borne out by the clinical trials that have been reported thus far. This article offers an overview of those hyperalgesic conditions in which NK1 receptor antagonists may be of therapeutic value and discusses possible reasons for the discrepancies between preclinical and clinical trials with NK1 receptor antagonists.
    MeSH term(s) Analgesics/pharmacology ; Animals ; Humans ; Neurokinin-1 Receptor Antagonists ; Pain/drug therapy ; Pain/physiopathology ; Substance P/physiology
    Chemical Substances Analgesics ; Neurokinin-1 Receptor Antagonists ; Substance P (33507-63-0)
    Language German
    Publishing date 2002-05-31
    Publishing country Germany
    Document type English Abstract ; Journal Article ; Review
    ZDB-ID 260-4
    ISSN 1432-055X ; 0003-2417
    ISSN (online) 1432-055X
    ISSN 0003-2417
    DOI 10.1007/s00101-002-0296-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Multidrug-resistance gene 1-type p-glycoprotein (MDR1 p-gp) inhibition by tariquidar impacts on neuroendocrine and behavioral processing of stress.

    Thoeringer, Christoph K / Wultsch, Thomas / Shahbazian, Anaid / Painsipp, Evelin / Holzer, Peter

    Psychoneuroendocrinology

    2007  Volume 32, Issue 8-10, Page(s) 1028–1040

    Abstract: The multidrug-resistance gene 1-type p-glycoprotein (MDR1 p-gp) is a major gate-keeper ... In addition, MDR1 p-gp has been found to control the intracerebral access of glucocorticoid hormones and ... of glucocorticoids in the control of behavior, we examined how acute pharmacological inhibition of MDR1 p-gp ...

    Abstract The multidrug-resistance gene 1-type p-glycoprotein (MDR1 p-gp) is a major gate-keeper at the blood-brain barrier (BBB), protecting the central nervous system from accumulation of toxic xenobiotics and drugs. In addition, MDR1 p-gp has been found to control the intracerebral access of glucocorticoid hormones and thus to modulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) system. In view of the implication of glucocorticoids in the control of behavior, we examined how acute pharmacological inhibition of MDR1 p-gp at the BBB by tariquidar (XR9576; 12 mg/kg, PO) impacts the neuroendocrine and behavioral processing of stress in C57BL/6JIcoHim inbred mice. Inhibition of MDR1 p-gp at the BBB did not alter emotional behavior at baseline. However, mice that were sensitized by water-avoidance stress, a mild psychological stressor, displayed significantly reduced anxiety-related behavior in the elevated plus-maze test when treated with tariquidar. Tariquidar, however, had no effect on stress-coping performance assessed in the forced swim test. Investigating the impact of acute MDR1 p-gp inhibition on the glucocorticoid system, we observed a significant attenuation of the mild stress-induced increase of plasma corticosterone after tariquidar administration. In order to examine whether the anti-anxiety effect of tariquidar in sensitized animals is mediated by glucocorticoids, the animals were treated with corticosterone (1mg/kg, SC) immediately after exposure to water-avoidance stress. Corticosterone caused a significant anxiolytic-like effect in this stress-related anxiety protocol, whereas tariquidar could not further enhance corticosterone's anti-anxiety effects. The current data show for the first time that pharmacological inhibition of MDR1 p-gp at the murine BBB by tariquidar alters emotional behavior and HPA axis activity. By facilitating the entry of corticosterone into the brain, tariquidar enhances feedback inhibition of the HPA system and in this way improves anxiety-related stress processing. These findings highlight a novel approach to the treatment of stress-related affective disorders in humans.
    MeSH term(s) ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors ; Adaptation, Psychological/drug effects ; Animals ; Anxiety/metabolism ; Anxiety/physiopathology ; Avoidance Learning/drug effects ; Behavior/drug effects ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/physiology ; Corticosterone/pharmacology ; Emotions/drug effects ; Glucocorticoids/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurosecretory Systems/drug effects ; Quinolines/pharmacology ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology ; Swimming
    Chemical Substances ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Glucocorticoids ; Quinolines ; tariquidar (J58862DTVD) ; Corticosterone (W980KJ009P)
    Language English
    Publishing date 2007-09-19
    Publishing country England
    Document type Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 197636-9
    ISSN 1873-3360 ; 0306-4530
    ISSN (online) 1873-3360
    ISSN 0306-4530
    DOI 10.1016/j.psyneuen.2007.08.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book ; Thesis: Analyse postoperativer funktioneller Ergebnisse von phaken Vorderkammerlinsen unterschiedlichen Typs

    Pechar, Viola / Holzer, Mike P.

    2018  

    Institution Universität Heidelberg
    Author's details vorgelegt von Viola Pechar ; Doktorvater: Prof. Dr. med. Mike P. Holzer
    Language German
    Size 96 Blätter, Illustrationen, Diagramme, 30 cm
    Publishing place Heidelberg
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Ruprecht-Karls-Universität Heidelberg, 2018
    HBZ-ID HT020204373
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2019 E 1108 order for loan Magazin

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  7. Article: Involvement of nitric oxide in the substance P-induced inhibition of intestinal peristalsis.

    Holzer, P

    Neuroreport

    1997  Volume 8, Issue 13, Page(s) 2857–2860

    Abstract: Although considered as an intestinal motor stimulant, substance P can inhibit intestinal ... was examined in luminally perfused segments of isolated guinea-pig ileum. Substance P (100 nM) and ... the NK1 receptor agonist substance P methyl ester (100 nM) increased the intraluminal pressure threshold ...

    Abstract Although considered as an intestinal motor stimulant, substance P can inhibit intestinal peristalsis via stimulation of tachykinin NK1 receptors. Since NK1 receptors are present on enteric nitrergic neurones, the contribution of nitric oxide (NO) to the peristaltic motor inhibition caused by tachykinins was examined in luminally perfused segments of isolated guinea-pig ileum. Substance P (100 nM) and the NK1 receptor agonist substance P methyl ester (100 nM) increased the intraluminal pressure threshold at which peristaltic contractions were elicited. This inhibitory influence on peristalsis was prevented by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (300 microM) in an enantiomer-selective manner. It is concluded that the substance P/NK1 receptor-mediated depression of intestinal peristalsis involves inhibitory motor pathways utilizing NO as a transmitter.
    MeSH term(s) Animals ; Enzyme Inhibitors/pharmacology ; Female ; Guinea Pigs ; Ileum/drug effects ; In Vitro Techniques ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/physiology ; Peristalsis/drug effects ; Receptors, Neurokinin-1/agonists ; Stereoisomerism ; Substance P/analogs & derivatives ; Substance P/pharmacology
    Chemical Substances Enzyme Inhibitors ; Receptors, Neurokinin-1 ; Nitric Oxide (31C4KY9ESH) ; Substance P (33507-63-0) ; substance P, methyl ester- (76260-78-1) ; NG-Nitroarginine Methyl Ester (V55S2QJN2X)
    Language English
    Publishing date 1997-09-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1049746-8
    ISSN 1473-558X ; 0959-4965
    ISSN (online) 1473-558X
    ISSN 0959-4965
    DOI 10.1097/00001756-199709080-00011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Warum versagen Substanz P(NKI)-Rezeptorantagonisten in der Schmerztherapie?

    Herbert, M. K. / Holzer, P.

    Der Anaesthesist

    2002  Volume 51, Issue 4, Page(s) 308

    Language German
    Document type Article
    ZDB-ID 260-4
    ISSN 0003-2417
    Database Current Contents Medicine

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  9. Article: Gut Signals and Gut Feelings: Science at the Interface of Data and Beliefs.

    Holzer, Peter

    Frontiers in behavioral neuroscience

    2022  Volume 16, Page(s) 929332

    Language English
    Publishing date 2022-07-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452960-6
    ISSN 1662-5153
    ISSN 1662-5153
    DOI 10.3389/fnbeh.2022.929332
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  10. Article ; Online: Different functions of the common P/V/W and V-specific domains of rinderpest virus V protein in blocking IFN signalling.

    Chinnakannan, Senthil K / Holzer, Barbara / Bernardo, Beatriz Sanz / Nanda, Sambit K / Baron, Michael D

    The Journal of general virology

    2013  Volume 95, Issue Pt 1, Page(s) 44–51

    Abstract: ... terminal 75 % being common to the viral P, V and W proteins, and not highly conserved between viruses ...

    Abstract The V proteins of paramyxoviruses are composed of two evolutionarily distinct domains, the N-terminal 75 % being common to the viral P, V and W proteins, and not highly conserved between viruses, whilst the remaining 25 % consists of a cysteine-rich V-specific domain, which is conserved across almost all paramyxoviruses. There is evidence supporting a number of different functions of the V proteins of morbilliviruses in blocking the signalling pathways of type I and II IFNs, but it is not clear which domains of V are responsible for which activities and whether all these activities are required for effective blockade of IFN signalling. We have shown here that the two domains of rinderpest virus V protein have distinct functions: the N-terminal domain acted to bind STAT1, whilst the C-terminal V-specific domain interacted with the IFN receptor-associated kinases Jak1 and Tyk2. Effective blockade of IFN signalling required the intact V protein.
    MeSH term(s) Animals ; Cell Line ; Humans ; Interferons/genetics ; Interferons/metabolism ; Janus Kinase 1/genetics ; Janus Kinase 1/metabolism ; Phosphorylation ; Protein Structure, Tertiary ; Rinderpest/enzymology ; Rinderpest/genetics ; Rinderpest/metabolism ; Rinderpest/virology ; Rinderpest virus/chemistry ; Rinderpest virus/genetics ; Rinderpest virus/metabolism ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism ; Signal Transduction ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/metabolism
    Chemical Substances STAT1 Transcription Factor ; STAT1 protein, human ; V protein, Paramyxovirus ; Viral Proteins ; Interferons (9008-11-1) ; Janus Kinase 1 (EC 2.7.10.2)
    Language English
    Publishing date 2013-10-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/vir.0.056739-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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