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  • 1995-1999  (1,169)
  • 1998  (1,169)
  • Theoretical, Physical and Computational Chemistry  (583)
  • Organic Chemistry  (362)
  • Rat  (170)
  • Inorganic Chemistry
  • Nuclear reactions
  • crystal structure
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  • 1995-1999  (1,169)
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Keywords
  • 1
    ISSN: 1534-4681
    Keywords: IL-6 ; Metastasis ; Hepatocellular carcinoma ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Previous studies demonstrated that excess IL-6 production correlated with the metastatic potential of rat hepatocellular carcinoma cells. In the work reported here a retroviral construct containing the gene for murine IL-6 was introduced into otherwise nonmetastatic tumor cells to directly determine the effect of IL-6 overexpression on tumor metastatic potential. Methods: The clonal cell lines 1682.C.2.9.L0 (L0, poorly metastatic) and 1682.C.2.9.L10 (L10, highly metastatic) were selected from a parental hepatocellular carcinoma induced in ACI rats by feeding an ethionine-containing diet. Viral supernatant was used to infect the PA317 amphotropic cell line, and retrovirus produced from these cells infected the poorly metastatic L0 hepatocellular carcinoma cell line. Neomycin-resistant cells were selected in G418 and designated L0-IL-6. Results: As determined by bioassay, L0 cells produce 10±1.2 U/mL IL-6 in culture, whereas L10 cells release 95±11 U/mL (P〈0.01, Student'st-test). Retroviral-mediated IL-6 gene transfer resulted in the production of 1266±48 U/mL IL-6 by L0-IL-6 cells under identical culture conditions. When an inoculum of 5×106 cells is injected subcutaneously, both L0 and L10 cell lines result in primary tumors with equivalent rates of growth; only L10 cells metastasize to the lung, however. A similar inoculation of L0-IL-6 cells produced local tumors in all 24 animals tested. Interestingly, 15 of 24 (62%) animals presented with metastatic nodules in the abdominal cavity, whereas no such tumors were found in animals receiving L10 cells. Conclusion: Overexpression of IL-6 increases metastatic potential of tumor cells, with preferential metastases to the abdominal cavity when compared with tumor cells elaborating endogenous IL-6.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 11-15 
    ISSN: 1572-8854
    Keywords: Mebendazole–propionic acid complex ; molecular complex ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Recrystallization of the anthelmintic drug mebendazole from propionic acid yields a 1:1 molecular complex which crystallizes in the triclinic system space group $${P\bar 1}$$ , a = 5.928(2), b = 11.066(2), c = 14.337(6)Å, α = 94.89(3), β = 101.56(3), γ = 96.18(2)°, and Z = 2 complex units in the unit cell. An x-ray diffraction study revealed an R 2 2 (8) hydrogen bonding system in the complex, involving the unprotonated imidazole N and amide N–H function of the drug and the acid carboxylic group. Complex molecules form centrosymmetric dimers by intermolecular N–H···O hydrogen bonding involving the protonated imidazole N atom and the benzoyl O atom of the drug molecule.
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  • 3
    ISSN: 1572-8854
    Keywords: Cu(II) complex ; crystal structure ; EPR spectra
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title compound, Cu(glyglygly)Br·1·5H2O, crystallizes in the space group C2/c, with a = 21.468(7), b = 6.716(5), c = 16.166(6) Å, β = 98.39°, and Z = 8. The tripeptide is bonded to one Cu(II) ion through the nitrogen [Cu–N=1.97(1)Å] and oxygen [Cu–O=2.019(8)Å] atoms of the amino end glycine residue and to another Cu(II) through one oxygen atom [Cu–O=1.931(9)Å] of the terminal carboxyl group. This give rise to covalently bonded and infinite ···–Cu–tripeptide–Cu–··· chains. These chains are linked to one another by a network of H-bonds involving the water molecules and bromide ions. The Cu(II) ion is in a distorted tetragonal pyramidal coordination polyhedron. At the corner of the base of the pyramid are the terminal glycine nitrogen and oxygen atoms of one tripeptide, a carboxylic oxygen of another tripeptide and a bromide ion. The fivefold coordination is completed with a water molecule at the top of the pyramid [Cu–Ow=2.286(9)Å]. For all orientations of the applied magnetic field the single crystal EPR spectra display a single anisotropic exchange collapsed resonance without hyperfine structure. Its position was measured in three perpendicular planes and the crystal g-tensor evaluated from the data. This tensor is interpreted in terms of the contributing Cu(II) complexes in the unit cell to deduce the principal values g1 = 2.273, g2 = 2.050 and g3 = 2.131 for the molecular gyromagnetic tensor. We also discuss the magnitude of the exchange interaction between neighboring copper ions in the lattice on the basis of the features in the EPR spectra and the structural information.
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  • 4
    ISSN: 1572-8854
    Keywords: 2-Methylnaphthalene ; hexachlorocyclopentadiene ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract 2-Methylnaphthalene undergoes Diels-Alder addition and substitution with hexachlorocyclopentadiene to give two products, 1,2,3,4,5,6,7,8,13,13,14,14-dodecachloro-1,4,4a,4b,5,8,8a,12b-octahydro-10-methyl-1,4;5,8-dimethanotriphenylene 1 and 1,2,3,4,5,6,7,8,13,13,14,14-dodecachloro-1,4,4a,4b,5,8,8a,12b-octahydro-10-(1′,2′,3′,4′,5′-pentachlorocyclopentadienyl)methyl-1,4;5,8-dimethanotriphenylene 2. The molecular structure of 2 has been characterized by X-ray crystallography: C26H9Cl17, monoclinic, space group P21/c, with a = 15.316(3), b = 13.698(3), c = 16.116(3) Å, β = 96.113(3)°, and Z = 4.
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  • 5
    ISSN: 1572-8854
    Keywords: Halobismuthate(III) ; phenanthroline ; synthesis ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The reaction between bismuthate oxide and phen (1,10-phenanthroline) in acid medium led to the isolation of the unusual [(PhenH)(PhenH2)][BiCl6]·2H2O derivative, which has been characterized by X-ray analysis and IR spectroscopy. The compound crystallizes in the triclinic space group $$[\text[P\bar 1]]$$ with a = 8.313(2), b = 9.349(2), c = 9.807(3) Å, α = 86.39(3), β = 110.27(3) and γ = 106.48(3)°. The crystal structure is made of [BiCl6]3− anions and [(PhenH)(PhenH2)]3+ cations. A network of hydrogen bond interactions involving the two clathrated water molecules, the phenanthroline moiety and the chlorines characterizes the entire structure.
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  • 6
    ISSN: 1572-8854
    Keywords: Lanthanum complex ; hexamethylenetetramine ; IR spectra ; thiocyanates ; coordination number nine ; tricapped trigonal prism ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title compound (LaC15H42N11O9S3) was prepared and characterized by means of X-ray, IR and Raman measurements. The crystals are orthorhombic: Pnma (No. 62), a = 21.117(2), b = 14.736(2), c = 10.082(1) Å, and Z = 4. The structure consists of polyhedra with a La(III) ion in the center of them and hexamethylene molecules, which link these polyhedra. Each La(III) ion coordinates seven molecules of water and two thiocyanate ions via nitrogen atoms. The IR and Raman spectra, which have been obtained and interpreted, are in good agreement with X-ray results.
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  • 7
    ISSN: 1572-8854
    Keywords: Cerium(IV) ; β-diketonate ; volatility ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The cerium(IV) β-diketonate compounds [Ce(β-diket)4] [where β-diket = tmhd (2,2,6,6-tetramethylheptane-3,5-dionate) 1, pmhd (1-phenyl-5-methylhexane-1,3-dionate) 2] were prepared by reacting cerium(IV) ammonium nitrate [CAN; Ce(NH4)2(NO3)6] with the respective Na(β-diket) compound in ethanol, and structurally characterized by single crystal X-ray diffraction. Compound 1 crystallizes in the triclinic space group $$P \bar 1$$ with a = 12.472(4), b = 19.972(5), c = 21.436(3) Å, α = 97.05(7), β = 90.16(2), γ = 106.55(3)°, V = 5076(2) Å3, Z = 4, T = 150(2) K. Compound 2 crystallizes in the monoclinic space group P21/n. with a = 14.817(6), b = 17.123(6), c = 19.146(3) Å, β = 105.46(4)°, V = 4682(3) Å3, Z = 4, T = 150(2) K. Crystals of 1 contain two independent [Ce(tmhd)4] molecules, with four chelating tmhd ligands bonded to each metal in a distorted dodecahedral arrangement; the cerium atom in 2 is also bonded to four chelating pmhd ligands but in this case the coordination geometry is closer to square antiprism. Both complexes are air and moisture stable. Sublimation studies reveal that 1 sublimes almost quantitatively, while 2 is comparatively involatile.
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  • 8
    ISSN: 1572-8854
    Keywords: Nickel(II) complex ; crystal structure ; Schiff base
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract A nickel(II) complex of the pyridine-2-aldehyde Schiff base of S-methyldithiocarbazate (HNNS) has been synthesized and characterized by means of elemental analysis, IR and UV-vis spectra. The crystal structure of the complex has been determined by single-crystal X-ray diffraction. The complex crystallizes in the monoclinic, space P21/c, with a = 14.092(2), b = 16.886(2), c = 8.857(2)Å; β = 105.78(3) °, V = 2028.2(6) Å3, and Z = 4. The nickel atom is octahedrally coordinated by two uninegatively charged tridentate Schiff base in a mer-configuration via the pyridine nitrogen atom, azomethine nitrogen atom, and mecaptide sulfur atom.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 885-892 
    ISSN: 1572-8854
    Keywords: Benztropine mesylate ; crystal structure ; thermal analysis ; dehydration kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The crystal structure of benztropine mesylate has been determined. It is orthorhombic, Pbca, with a = 12. 885(8)Å, b = 32.012(9)Å, and c = 10.027(3) Å. It exhibits similar packing to that seen in the previously reported crystal structure of benztropine mesylate monhydrate. X-ray powder diffraction patterns have been used to identify the anhydrous and monohydrate forms. The dehydration of the monohydrate follows a first-order reaction mechanism with activation energy of 92(8) kJ mol−1.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 521-527 
    ISSN: 1572-8854
    Keywords: Cadmium ; crown ether ; 15-crown-5 ; 18-crown-6 ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Reaction of 15-crown-5 or 18-crown-6 in 3:1 (v/v) CH3CN:CH3OH with Cd(NO3)2·4H2O followed by slow evaporation produces [Cd(NO3)2(15-crown-5)] or [Cd(NO3)2(18-crown-6)]. Crystals of [Cd(NO3)2(15-crown-5)] are orthorhombic with space group Pbca and cell parameters a = 13.562(5), b = 15.941(9), and c = 15.011(7) Å at 295 K. [Cd(NO3)2(18-crown-6)] crystallizes in the monoclinic space group C2/c with a = 11.235(2), b = 11.196(5), c = 15.385(3) Å, and β = 99.89(2)° at 295 K. The metal center in [Cd(NO3)2(15-crown-5)] rests atop the macrocyclic donor array with two cis-bound nitrate anions and adopts a distorted tricapped trigonal prismatic geometry. [Cd(NO3)2(18-crown-6)] resides on an equatorial two-fold rotation axis with Cd2+ coordinated in the 18-crown-6 cavity and the nitrate anions oriented in twisted trans positions.
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  • 11
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 577-579 
    ISSN: 1572-8854
    Keywords: (−)—Crinine ; Pancratium ; alkaloid ; Amaryllidaceae ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract (−)—Crinine, C16H17NO3, is an alkaloid extracted from the bulbs of Pancratium maritimum L. (Amaryllidaceae). The compound crystallizes in the space group P212121 with cell dimensions a = 6.040(1), b = 12.382(1), c = 17.861(2) Å, with Z = 4. The molecule has five rings and an OH group. The N-containing, five-membered ring and the D ring have envelope conformations. The A and B rings have distorted chair and half-chair conformations, respectively.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 217-220 
    ISSN: 1572-8854
    Keywords: Metal carbonyl complexes ; chelate complexes ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The x-ray crystal structure of the complex η2-PDOW(CO)4 (five-membered ring, PDO = 2, 2, 4, 7, 7-pentamethyl-3,6-dithiaoctane) is reported. The complex crystallizes in the monoclinic crystal system, space group P21/c, [#14] with unit cell parameters a = 14.002(14) Å, b = 9.340(10) Å, c = 15.094(12) Å, β = 92.67(4)°, V = 1972(3) Å3; Z = 4. The arrangement of the ligands around the metal atom is distorted from octahedral geometry. Large C–O bond distances and short W–C bond distances of the carbonyl groups located at a trans position with respect to PDO is indicative of a trans influence. The W–S(1) and W–S(2) bond distances of 2.545(3) and 2.545(2) Å, respectively, are shorter than observed for closely related complexes.
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  • 13
    ISSN: 1572-8854
    Keywords: Triphenylsiloxy ; silanol ; borane ; crystal structure ; adduct
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title compound crystallizes in the triclinic space group $$P \bar 1$$ , with a = 14.458(6), b = 14.630(5), c = 14.721(8) Å, α = 79.75(2), β = 80.11(3), γ = 80.50(3)°, and Z = 2. The crystal structure consists of molecules of (Ph3SiO)3B and Ph3SiOH linked by an weak B···(silanol) acceptor-donor bond, additionally stabilized by OH(silanol)···O(siloxy) hydrogen bonds. The average B–O, Si–O distances and B–O–Si angle are 1.369, 1.649 Å and 137.2°, respectively.
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  • 14
    ISSN: 1572-8854
    Keywords: Steroid ; pregnadiene ; x-ray diffraction ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title compound is C29H34O4, tetragonal, P43, a = b = 10.310(1), c = 23.871(2)Å. The A, B, C, and D rings adopt envelope, half-chair, chair, and distorted chair conformations, respectively. The phenyl ring is planar. The methyl substituents at the A/B, C/D, and at C(17) are axial; and the –OCOCH3 group at C(17) and phenyl ring at C(16) are equatorial. The molecules in the crystal are held together by van der Waals forces and several C–H···O hydrogen bond interactions.
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  • 15
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 539-543 
    ISSN: 1572-8854
    Keywords: Antimalarial ; crystal structure ; peroxy bridge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The crystal and molecular structure of the antimalarial compound Artemisinin (formerly known as Qinghaosu), C15H22O5 has been determined by direct methods. Crystals are orthorhombic colorless needles, space group P212121, Z = 4. D c = 1.299 g cm −3, with unit cell parameters a = 6.3543(9), b = 9.439(3), c= 24.066(4) Å. The molecule incorporates a fused ring system containing a six-membered ring C which includes an oxygen bridge and a peroxy-bridge. The ring C has a distorted boat conformation and the C - O - O - C torsion angle is 47.8(2)°. Rings A and D have symmetrical chair and distorted chair conformations, repectively. Ring junctions A/B, A/D, and C/D are cis, junction B/D is trans. All inter-molecular contacts are van der Waals. The absolute configuration of Artemisinin was determined from the refined value of the Flack x parameter. [The atomic coordinates given in a previous structure analysis, “Crystal Structure and Absolute Configuration of Qinghaosu,” Qinghaosu Research Group, Institute of Biophysics, Academica Sinica, Scientia Sinica, Vol. XXIII No. 3, 380 (1980), do not display the molecule in its absolute configuration.]
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  • 16
    ISSN: 1572-8862
    Keywords: Ruthenium ; thioether macrocycle ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The reaction of a mixture of cis-3,7,11-trimethyl-1,5,9-trithiacyclododecane, cis-Me312S3, 1 and trans-3,7,11-trimethyl-l,5,9-trithiacyclododecane, trans-Me312S3, 2, with Ru6(CO)17(μ 6-C), 3, yielded three new cluster compounds Ru6(CO)13(μ-η3-cis-SCH2CHMe(CH2SCH2CHMe)2CH2)(μ 6-C) 4, and two isomers of Ru6(CO)13(μ-η3-cis-SCH2CHMe(CH2SCH2CHMe)2CH2)(μ 6-C) 5a and 5b. The molecular structures of 4 and 5b were established by single crystal X-ray diffraction analyses. In both complexes, the macrocycles have adopted tridentate coordination with one of the sulfur atoms in a bridging position. Two carbonyl ligands occupy bridging positions in each compound. Crystal Data for 4·Me2CO: space group=P21/n, a=11.295(1) Å, b=17.547(3) Å, c=20.318(3) Å, β=93.71(1)°, Z=4, 2900 reflections, R=0.025. Crystal Data for 5b·1.5 C6H6: space group=Pbca, a=31.8900(8) Å, b=23.4330(6) Å, c=21.6240(4) Å, Z=16, 12163 reflections, R=0.040.
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  • 17
    ISSN: 1572-8862
    Keywords: Mixed-metal cluster ; crystal structure ; magnetic properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The preparation, magnetic properties, and crystal structure of [(salen)Cu]4[(salen)Fe(H2O)2]2(ClO4)2 via hydrogen bonding are described [salen=N,N′-ethylenebis (salicylideneiminate)]. Crystals are triclinic, of space group $$\rm P\bar 1$$ , with cell constants a=12.853(3), b=13.921(3), c=14.251(3) Å, α=68.68(3)°, β=87.86(3)°, γ=86.82(3)°, and Z=1. The structure was solved and refined to R=0.064 and R′=0.068. The structure comprises the hexanuclear units which result from the linking of four mononuclear fragments [(salen)Cu] and two mononuclear fragment [(salen)Fe(H2O)]+, through Cu -O ⋯ H -O -Fe -O -H ⋯ O -Cu hydrogen bonds of coordinating H2O. In this complex, FeIII ions are in almost square-planar surroundings. The temperature dependences of the magnetic susceptibilities of the complex have been studied in the 4.2–300 K range, indicating the presence of an antiferromagnetic interactions between metal ions.
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  • 18
    ISSN: 1572-8862
    Keywords: Dynamic disorder ; crystal structure ; ruthenium cluster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The disorder in the X-ray crystal structures of Ru3(CO)11(L), L=CN t Bu 1 and PMe3 3 has been re-examined. Crystallographic data for 1 at 100 K: C16H9NO11Ru3, space group P21/n, a=11.796(5), b=11.748(2), c=16.040(7) Å, β=109.81(3)°, Z=4, 6077 reflections, R=0.028. For 3 at 223 K: C14H9O11PRu3, space group P21/n, a=8.5971(15), b=12.391(7), c=40.345(8) Å, β=94.43(2)°, Z=8, 7966 reflections, R=0.031. The disorder present in 1 and 3 at room temperature disappears reversibly on cooling, showing that it is dynamic in origin. The ligator atoms of the isonitrile and phosphine ligands move by a maximum of ∼0.8 Å, indicating that the whole cluster does not rotate intact within the crystal lattice, but rather that the Ru3 triangle effectively oscillates within a relatively rigid ligand polyhedron. The crystal structure of Ru3(CO)9{P(OMe)3 3} 7, which crystallizes in triclinic (7-t) and monoclinic (7-m) modifications is also reported. Both modifications have two independent molecules in the asymmetric unit, and both modifications display dynamic disorder in the metal framework. Crystalllographic data for 7-t at 173 K: C18H27O18P3Ru3, space group P-1, a=11.8085(18), b=15.915(2), c=17.350(3) Å, α=99.929(14), β=101.811(14), γ=90.630(12)°, Z=4, 11242 reflections, R=0.048. For 7-m at 120 K: C18H27O18P3Ru3, space group P21/c, a=11.708(8), b=15.922(5), c=33.950(10) Å, β=99.29(4), Z=8, 10191 reflections, R=0.027.
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Journal of applied electrochemistry 28 (1998), S. 559-563 
    ISSN: 1572-8838
    Keywords: electroless Ni–Co–B alloy ; dimethylamineborane ; complexing agent ; deposition rate ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Notes: Abstract Fundamental aspects of electroless Ni–B, Co–B and Ni–Co–B alloys have been systematically examined. The composition, crystal structure and deposition rate of the alloys were determined as a function of the concentration of reducing agent (dimethylamineborane) and complexing agents (tartrate, citrate, malonate and succinic acid), bath pH and Ni2+/Co2+ ratio. Changes in the deposition rate and metallurgical features of the alloys induced by the change in plating parameters are discussed, based on electrochemical polarization data and the formation enthalpy of the nickel and cobalt borides.
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  • 20
    ISSN: 1572-8854
    Keywords: Copper ; 1,10-phenanthroline ; trifluoroacetate ; crystal structure ; magnetic exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The compound [Cu(phen)(O2CCF3)2]n (phen = 1,10-phenanthroline) has been synthesized and its crystal structure determined. It crystallizes in monoclinic space group C2/c, with a = 19.229(7), b = 11.281(5), c = 7.621(2) Å, β = 104.305(12)°, and Z = 4. The crystal structure is polymeric, being built from infinite zigzag chains of trifluoroacetate bridged copper(II), with the phenanthroline ligands being stacked between the chains. The variable-temperature (13–300 K) magnetic susceptibility and ESR data are reported and a weak ferromagnetic exchange interaction is observed with the exchange parameter estimated as J = 2.9 cm−1.
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  • 21
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 839-841 
    ISSN: 1572-8854
    Keywords: π-allyl ; carbonyl ; nitrile ; chloro ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title compound crystallizes in the monoclinic spacegroup P21/m with a = 6.796(9), b = 12.145(14), c = 7.749(8)Å, β = 101.86(1)°, and Z = 2. The crystal structure consists of molecules of [MoCl(CO)2(NCMe)2(η3-C3H4Me-2)] with crystallographically imposed Cs symmetry and has a pseudo-octahedral geometry, with the π-allyl group trans- to the chloro group and the two cis-carbonyl and acetonitrile groups occupying the equatorial plane.
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  • 22
    ISSN: 1572-8854
    Keywords: 1,10-Phenanthroline ; bis-phenanthrolineprotium ; adduct ; crystal structure ; hydrogen bonding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Herzog's reported bis-1,10-phenanthrolineammonium perchlorate, [(phen)2(NH4)](ClO4) is in fact the known 2:1 adduct of l,10-phenanthroline (phen) with perchloric acid, [(phen)2H](CIO4). Its crystal structure, mode of formation, and properties are described. The compound crystallizes in the triclinic space group with $$P\bar 1$$ , a = 7.2510(8), b = 13.120(2), c = 22.083(12) Å, α = 77.4550(12), β = 84.45(2), γ = 82.204(14)°, V = 2026.7(6) Å3, Z = 4, and D c = 1.510 g cm−3. It contains cationic columns of alternating 1,10-phenanthroline and its conjugate acid.
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  • 23
    Electronic Resource
    Electronic Resource
    Springer
    Journal of chemical crystallography 28 (1998), S. 645-648 
    ISSN: 1572-8854
    Keywords: 2-Bromoleptoclinidinone ; marine alkaloid ; cytotoxic ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract 2-Bromoleptoclinidinone methanol solvate, C18H8BrN3O·CH4O, crystallizes in the orthorhombic space group Pbca with a = 15.7013(2), b = 7.3308(1), and c = 26.9326(1) Å. The molecule is essentially planar, with the largest deviations occurring at bromine (−0.21 Å), carbonyl oxygen O(l) (+0.19 Å) and in ring-A (C(9) −0.15 Å, C(10) −0.15 Å). Methanol occupies the 1,10-phenanthroline-like metal binding site of the title compound.
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  • 24
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    Journal of chemical crystallography 28 (1998), S. 925-929 
    ISSN: 1572-8854
    Keywords: Quinoline ; chloroquine ; antimalarial ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The preparation of N12-(7-chloro-4-quinolinyl)-N 1,N 1-diethyl-1,12-diaminododecane, AQ-40, was accomplished by a five-step process in 80% overall yield from 12-aminododecanoic acid and 4,7-dichloroquinoline. AQ-40 crystallizes as a monohydrate from reagent grade chloroform/ diethyl ether mixtures in the triclinc space group P-1 with a = 8.667(2), b = 8.9425(10), c = 17.217(3) Å, α = 99.34(1), β = 99.89(2), γ = 91.56(1)°, V = 1295.0 Å3 and Z = 2. The l2-(N 1,N 1-diethylamino)dodecyl side chain is in the fully extended conformation and the water molecule forms hydrogen bonds to the two tertiary nitrogen atoms as well as with the secondary amino group. The nitrogen of the secondary amino group bound to the four-position of the quinoline moiety is virtually planar. This together with the rather short C–N distance of 1.347(3) Å to the quinoline moiety suggests involvement of the lone pair on this nitrogen with the π system of the ring.
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  • 25
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    Journal of chemical crystallography 28 (1998), S. 69-72 
    ISSN: 1572-8854
    Keywords: Co(III) complex ; crystal structure ; kinetics ; steric effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title compound crystallizes in the orthorhombic space group Pnma, with a = 7.9209(5), b = 9.818(1), c = 16.867(2) Å, and Z = 4. The structure was solved employing 1864 independent x-ray reflections with I〉2σ(I) by Patterson and difference Fourier techniques and refined by full-matrix least-squares to R = 0.036. The trans-[CO(NH3)4(NH2CH3)Cl](ClO4)2 molecule is on a crystallographic mirror plane. The cobalt ion is in an elongated octahedral coordination with four equatorial ammonia ligands [average Co–N distance equal to 1.966(2) Å], an axial methylamine [Co–N=1.965(3)Å], and an axial chlorine ion [Co–Cl=2.2771(9)Å]. Kinetic steric effects of the complex are interpreted in terms of structural results.
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  • 26
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    Journal of chemical crystallography 28 (1998), S. 209-212 
    ISSN: 1572-8854
    Keywords: Bismuth ; crystal structure ; inorganic polymer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The ethylenediammonium pentachlorobismuthate(III) dihydrate salt is monoclinic with the following unit cell dimensions: a = 10.902(8)Å, b = 7.926(6)Å, c = 15.199(6)Å, β = 96.40(1)°, space group P21/n with Z = 4. The structure shows a layer arrangement parallel to the $$\vec a$$ axis: planes of the [Bi2Cl10]4− bioctahedra alternate with planes of [NH3(CH2)2NH3]2+ dications. The [Bi2Cl10]4− bioctahedra are connected through O(W)–H··· Cl hydrogen bonds, so that infinite unidimensional chains of composition [Bi2Cl10(H2O)2] n 4n− are formed in the structure parallel to the $$\vec a$$ axis. These chains are themselves interconnected by means of the N–H···Cl bonds originating from the [NH3(CH2)2NH3]2+ entities, forming a three-dimensional network.
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  • 27
    ISSN: 1572-8854
    Keywords: Strontium ; triphenylsiloxy ; crystal structure ; ammonia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The title complex [Sr2(OSiPh3)4(NH3)5]·0.5C7H8 was prepared by the reaction of strontium metal granules with triphenylsilanol in an ammoniacal-toluene solution at −40°C. It crystallizes in monoclinic space group P21/n with a = 14.465(3), b = 20.715 (6), c = 25.199(6) Å, β = 95.98(2)°, and Z = 4. The complex has a dimeric structure with one terminal and three bridging triphenylsiloxy ligands, the remaining coordination sites being occupied by five ammonia molecules. The central Sr2O4N5 moiety adopts a distorted M2X9 face-sharing bioctahedral arrangement.
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  • 28
    ISSN: 1572-8854
    Keywords: Mixed rubidium–ammonium acid sulfate ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The structure of Rb0.7(NH4)0.3HSO4 has been determined by X-ray analysis. The mixed compound crystallizes in the monoclinic space group P21/n with unit cell parameters a = 14.374(6) Å, b = 4.618(6) Å, c = 14.412(2) Å, β = 118.03(2)°, V = 844.4(4) Å3, and D cal = 1.536 g cm−3 for Z = 8. The mixed compound Rb0.7(NH4)0.3HSO4 is a chain-based structure. The Rb+ and NH4 + cations are intercalated between chains, formed of HSO4 - groups linked with OH⋯O hydrogen-bonding. Rb0.7(NH4)0.3HSO4 presents a new type of structural arrangement different from those of pure RbHSO4 and NH4HSO4.
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  • 29
    ISSN: 1572-8854
    Keywords: 2-[1,5-Dimethyl-4-hexenyl]-6-hydroxy-5-methyl-1,4-benzoquinone ; 2-[1,5-dimethyl-4-hexenyl]-6-amino-3-hydroxy-5-methyl-1,4-benzoquinone ; 2-[1,5-dimethyl-4-hexenyl]-3-amino-6-hydroxy-5-methyl-1,4-benzoquinone ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The crystal structures of isoperezone (1), aminoperezone (2), and isoaminoperezone (3) have been determined by single-crystal X-ray diffraction. Compound (1) yields orange crystals, orthorhombic space group P212121 with unit cell dimensions a = 6.271(6), b = 30.373(7), c = 7.257(1) Å, and Z = 4; compound (2) yields purple crystals, orthorhombic space group P212121 with unit cell dimensions a = 6.498(3), b = 7.500(1) c = 29.200(6) Å, and Z = 4; compound (3) yields purple crystals, monoclinic space group P21 with unit cell dimensions a = 7.354(1), b = 7.511(1), c = 13.283(1) Å, β = 102,07(1)°, and Z = 2. The side chains in (1)–(3) are oriented out of the plane of the quinone ring at an angle of 124, 144, and 97°, respectively. The molecules in the crystal are held together by hydrogen-bonding networks and van der Waals interactions.
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  • 30
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    Journal of chemical crystallography 28 (1998), S. 639-643 
    ISSN: 1572-8854
    Keywords: Tungsten(II) ; diiodo ; carbonyl ; trimethylphosphite ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract [WI2(CO)3{P(OMe)3}2]crystallizes in the orthorhombic space group Pca21, with a = 26.924(5), b = 10.726(2), c = 14.136(3) Å, and Z = 8. There are two molecules in the asymmetric unit, the metal atoms in each case being seven-coordinate with a capped fac-(CO)3 octahedral geometry. The molecular dimensions in the two molecules are nearly identical. The W–P distance to the capping atom 2.397 Å (average) is significantly shorter than the other W–P distance, 2.525 Å (average).
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  • 31
    ISSN: 1572-8854
    Keywords: Pyrimidine ; carboxamide ; sulfonyl ; chiral ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract Three novel dihydropyrimidine compounds N8,6-di(4-nitrophenyl)-(3R)-ethyl-(7R)-methyl-5-oxo-2,3,6,7-tetrahydrooxazolo[3,2,c] pyrimidine-8-carboxamide (2), N8,6-di((4-methylphenyl)-sulfonyl)-(3R)-ethyl-5-oxo-(7R)-phenyl-2,3,6,7-tetrahydrooxazolo [3,2,c]pyrimidine-8-carboxamide (3) and N8,6-di ((4-methylphenyl)sulfonyl)-(3R)-ethyl-(7R)-methyl-5-oxo-2,3,6,7-tetrahydrooxazolo[3,2,c] pyrimidine-8-carboxamide (4) have been prepared (from 2-amino-1-butanol of 64.4% e.e.) and structurally characterized by X-ray crystallography. All three compounds contain stereogenic centers, but the crystal of (2) chosen was found to be racemic whilst those of (3) and (4) were found to be homochiral. Compound (2) crystallizes in the monoclinic space group P21/c, with a = 17.958(4), b = 12.431(2), c = 9.653(2) Å, β = 96.20(3)°, U = 2142.3(7) Å3, Z = 4, and D c = 1.449 g cm−3. Compounds (3) and (4) both crystallize in the monoclinic space group P21, with a = 9.349(2), b = 5.824(5), c = 26.513(8) Å, β = 99.43(2)°, U = 1424.1(13) Å3, Z = 2 and D c = 1.389 g cm−3 for (3), and a = 5.9526(9), b = 16.3521(10), c = 13.2263(11) Å, β = 92.81(12)°, U = 1285.9(2) Å3, Z = 2 and D c = 1.378 g cm−3 for (4).
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  • 32
    ISSN: 1572-8854
    Keywords: Heterotrimetallic sulfido cluster ; linear ; synthesis ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The complex Cu(PPh3)3I reacts with [Et4N]2MoS4 and FeBr2 to give the heterotrimetallic complexes [Et4N][(Ph3P)2{CuS2MoS2Fe}Br2] (1). [Et4N][(Ph3P)2{CuS2MoS2Fe}Br2] (1) crystallizes in the triclinic space group P-1, a = 13.537(4), b = 15.316(4), c = 12.381(4) Å, α = 105.16(2), β = 93.27(3), γ = 101.18(2)°, and V = 2415.0(12) Å3 for Z = 2. The three metal atoms of the structure [Et4N][(Ph3P)2{CuS2MoS2Fe}Br2] (1) are nearly distributed along a line, where three metal atoms (Mo, Cu, Fe) are each in an approximate tetrahedral coordination, the lengths Mo-Fe and Mo-Cu distances are 2.772(2) and 2.798(2) Å, respectively.
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  • 33
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    Journal of chemical crystallography 28 (1998), S. 447-452 
    ISSN: 1572-8854
    Keywords: Bimetallic EDTA complex ; crystal structure ; antimony
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The synthesis and crystal structure of a new EDTA complex, [CaSb2(EDTA)2(H2O)8]n, are reported. This compound crystallizes in the monoclinic space group P21/n, with a = 7.132(1) Å, b = 21.893(3) Å, c = 10.891(2) Å, β = 91.15(2)°. Sb(EDTA) entities are connected through carboxylate bridges to the calcium atoms resulting in layers parallel to the (101) plane. These layers are linked through a weak Sb···O bond (3.171 Å). Pyrolysis of this complex under sulfur vapor, between 400 and 800°C, leads to a mixture of the monometallic sulfides. Pyrolysis in air above 700°C allows the easy preparation of the mixed oxide CaSb2O6.
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  • 34
    ISSN: 1572-8854
    Keywords: 1-1′-Diphosphaferrocene conformation ; P···P secondary bonding ; bis-[W(CO)5](l,l′-diphosphaferrocene system) ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract The structures of (3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocen-2-yl)carboxylic acid (1) and its bis-[W(CO)5] pentane solvate complex (2) have been determined by X-ray analysis. The compound 1 crystallizes in the monoclinic P21 /n space group with Z = 4; a = 7.8404(9), b = 14.9441(16), c = 11.7730(14) Å, β = 92.773(10)°, V = 1377.8(3) Å3, and Dcalc = 1.553 g cm−3. The compound 2 crystallizes in the triclinic $$P\bar 1$$ space group with two complex molecules and one pentane molecule in the unit cell. Cell parameters: a = 10.7070(2), b = 12.577(2), c = 13.239(3) Å, α = 84.00(2), β = 77.58(1), γ = 66.06(1)°, V = 1591.0(5) Å3, and Dcalc = 2.100 g cm−3 .The fully eclipsed conformation of the phospholyl rings with P···P secondary bonding of 3.353(1) Å is observed in 1 and a partially eclipsed conformation is found in 2. The 10 possible conformations of 1,1′-diphosphaferrocenes were described as the function of conformational parameter θ and observed geometry of the phospholyl rings.7 We suppose that the earlier conclusions concerning the destabilizing nature of 1,1′-diphosphaferrocene conformations with θ 〈 100° cannot be considered as general. The mode of W – P coordination, the structural changes of 1 by W(CO)5 coordination, the structural effect of phospholyl rings substitution by the –COOH group, and hydrogen bonds are analyzed.
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  • 35
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    Journal of chemical crystallography 28 (1998), S. 635-638 
    ISSN: 1572-8854
    Keywords: Cobalt(II) ; 2-aminobenzenethiol ; trimethylphosphite ; crystal structure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences , Physics
    Notes: Abstract A cobalt-thiolato-phosphite complex [Co(o-SC6H4NH2){P(OMe)3}3]PF6 has been prepared and characterized by X-ray crystallography. The complex crystallizes in the triclinic space group $$P\bar 1$$ with a = 10.590(4), b = 11.122(3), c = 13.577(5) Å, α = 101.85(1), β = 108.50(1), γ = 101.75(1)°, V = 1420.6(8) Å3, and Z = 2. The structure comprises discrete [Co(o-SC6H4NH2){P(OMe)3}3]+ cations and PF 6 − anions where the metal atom is coordinated in a highly distorted square-pyramidal environment by one chelate o-SC6H4NH 2 − (abt) and two P(OMe)3 ligands in the basal positions, and a third P(OMe)3 in the axial site with Co–N,, 1.847(5), Co–S, 2.166(2), Co–P, 2.157(2), 2.147(2), and 2.125(2) Å.
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  • 36
    ISSN: 1572-8862
    Keywords: Silver cluster ; crystal structure ; tetrameric cluster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract The sought-after member of the [(PDBP) n AgX] m (n, m=1,4; 2,2; 3,1; PDBP=5-Phenyldibenzophosphole, X=halides) series, the tetrameric [(PDBP)AgCl]4 cluster has been prepared and structurally characterized. The [P4Ag4Cl4] cluster core of [(PDBP)AgCl]4 bears striking similarity to that of [(Ph3P)AgCl]4.
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  • 37
    ISSN: 1438-2199
    Keywords: Amino acids ; 14C-l-Serine ; Rat ; Whole body autoradiography ; Accumulation ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of radioactivities in rats following intravenous administration of14C-d- or -l-serine was investigated by whole body autoradiography. The radioactivities were distributed throughout the whole body in both cases with the greatest amount being found in the pancreas. D- andl- Serine levels in the pancreas were determined by high-performance liquid chromatography with a chiral column which revealed, for the first time, the existence ofd-serine in the rat pancreas (12.6 ± 7.90 nmol/g wet tissue) together with a much higher concentration (924 ± 116 nmol/g) ofl-serine. The results suggested that exogenous D-serine of dietary origin contributed at least in part to the D-serine levels found in mammalian tissues. The accumulation of radioactivity in the kidney, especially in the corticomedullary area, even at 24 hr after administration of14C-l-serine suggested a possible link between acute necrosis of the renal proximal tubules and the administration of a large dose of D-serine [Am J Pathol 77: 269–282 (1974)].
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  • 38
    ISSN: 1438-2199
    Keywords: Amino acids ; In situ hybridization ; Cysteine dioxygenase ; Liver ; Lung ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied byin situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.
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  • 39
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Rat ; Natriuresis ; Hypotonic saline ; Hypertonic saline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar-Kyoto rats were given either tap water (control) or 3%β-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50μl/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.
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  • 40
    ISSN: 1438-2199
    Keywords: Amino acids ; Striatal dopamine release ; Intrastriatal taurine ; GABA ; Homotaurine ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studiedin vivo the effects of locally infused taurine (50, 150, and 450 mM) on the striatal dopamine and its metabolites in comparison with those of GABA and homotaurine, a GABAA receptor agonist, in freely moving rats. The extracellular dopamine concentration was elevated maximally 2.5-, 2- and 4-fold by taurine, GABA and homotaurine, respectively. At 150 mM concentration, at which the maximum effects occurred, homotaurine increased the extracellular dopamine more than taurine or GABA. When taurine and GABA were infused simultaneously with tetrodotoxin the output of dopamine did not differ from that in the presence of tetrodotoxin alone. In comparison, tetrodotoxin did not inhibit the increase in extracellular dopamine caused by homotaurine. Furthermore, omission of calcium from the perfusion fluid inhibited the increase of extracellular dopamine caused by GABA. However, it did not block the increase of dopamine caused by taurine or homotaurine. The present study suggests that the effects of intrastriatal taurine, GABA and homotaurine on the striatal extracellular dopamine differ. Thus, these amino acids seem to affect the striatal dopaminergic neurons via more than one mechanism.
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  • 41
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    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 133-142 
    ISSN: 1432-1912
    Keywords: Key words Intimal hyperplasia ; Potassium chloride ; α1-Adrenoceptor ; Methacholine ; Sodium nitroprusside ; Rat ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of neointima formation on functional characteristics was investigated in rat carotid artery preparations. The process of intimal hyperplasia development in the injured carotid arteries was followed in time both morphologically and morphometrically. Simultaneously with the loss of endothelial cells due to the balloon injury procedure, the vasodilator responses to methacholine were abolished. The sensitivity for the α1-adrenoceptor agonist phenylephrine appeared to be increased only immediately after injury. The balloon injury method led to significant neointima formation in the rat left common carotid artery 14 days after the intervention. Eight weeks after balloon injury, the neointimal mass reached its maximum. Parallel to the development of intimal hyperplasia, the α1-mediated vasoconstrictor responses to phenylephrine were significantly impaired. After 12 weeks of observation, reoccurrence of mature endothelial cells on the luminal surface of the neointima could be observed. Simultaneously, the vascular responses to phenylephrine and methacholine recovered. The vasoconstrictor responses to high potassium concentrations (100 mM) as well as the vasodilator effects of sodium nitroprusside appeared to be uninfluenced by balloon injury throughout the period of observation. From this study we conclude that both the receptor-mediated contractile responses to α1-adrenoceptor stimulation and the endothelium-dependent vasodilator responses to methacholine become severely impaired as a consequence of balloon catheter injury followed by intimal hyperplasia. However, these pharmacological responses may fully recover upon a prolonged period of endothelial regeneration.
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  • 42
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    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 336-343 
    ISSN: 1432-1912
    Keywords: Key words NNK ; Elimination kinetics ; Metabolism ; Perfusion ; Lung ; Liver ; Rat ; N-oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen in all species tested. To elicit its tumorigenic effects NNK requires metabolic activation which is supposed to take place via α-hydroxylation, whereas N-oxidation is suggested to be a detoxification pathway. The differences in the organ specific metabolism of NNK may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore, metabolism of NNK was investigated in the target organ lung and in liver of Fischer 344 (F344) rats using the model of isolated perfused organs. High activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK was eliminated by liver substantially faster (clearance 6.9 ± 1.6 ml/min, half-life 14.6 ± 1.2 min) than by lung (clearance 2.1 ± 0.5 ml/min, half-life 47.9 ± 7.4 min). When the clearance is calculated for a gram of organ or for metabolically active cell forms, the risk with respect to carcinogenic mechanisms was higher in lung than in liver. The metabolism of NNK in liver yielded the two products of NNK α-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of NNK, which is one of the two possible pathways of α-hydroxylation, were detected in lung but not in liver perfusion. Formation of these metabolites (4-oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers were perfused with 150 μM NNK, equal to a dosage which is sufficient to induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35 nM NNK. Nevertheless, the main part of NNK was also transformed via α-hydroxylation for this high concentration of NNK.
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  • 43
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    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 593-599 
    ISSN: 1432-1912
    Keywords: Key words d-amphetamine ; Dopamine receptors ; Locomotor activity ; Raclopride ; SCH-23390 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In d-amphetamine-treated (4.0 mg kg–1 s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5–20.0 µg kg–1 s.c.) and raclopride (12.5–100.0 µg kg–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5 m2). Thus, at the low doses of SCH-23390 (2.5–10.0 µg kg–1) or raclopride (12.5–50.0 µg kg–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 µg kg–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 µg kg–1) and the corresponding raclopride-induced (12.5 µg kg–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 µg kg–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the α1-adrenoceptor antagonist prazosin (1.0 mg kg–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D1 and D2/3 receptors.
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  • 44
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    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 671-676 
    ISSN: 1432-1912
    Keywords: Key words Gastric emptying ; Nitric oxide ; Pregnancy ; Gastric fundus ; Pylorus ; Non-adrenergic non-cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of pregnancy on the role of nitric oxide (NO) in gastric emptying and in non-adrenergic non-cholinergic (NANC) relaxation was studied in rats. The gastric emptying of a non-nutrient liquid solution and of polysterene beads was studied in non-pregnant (NP), 6 to 7 days pregnant (P7) and 18 to 20 days pregnant (P20) rats. Longitudinal muscle strips of the gastric fundus and circular muscle strips of the pylorus were isolated from NP and P20 rats and NANC relaxations were induced by electrical field stimulation. The gastric emptying of the liquid meal was significantly increased in P20 rats as compared to NP and P7 rats. In NP rats, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently (50–150 mg/kg ip) reduced the gastric liquid emptying; the inhibitory effect of 100 mg/kg L-NAME ip was prevented by 400 mg/kg ip L-arginine and was mimicked by 100 mg/kg NG-monomethyl-L-arginine (L-NMMA). The percentage inhibition of the liquid emptying by L-NAME did not differ between the 3 groups, except for the dose of 150 mg/kg ip where it was significantly lower in P20 rats. The gastric emptying of beads was 54% in NP, 36% in P7 and 69% in P20 rats but these values were not significantly different illustrating the great variability. The inhibitory effect of L-NAME (25 and 100 mg/kg ip) on the emptying of beads did not differ between the 3 groups. As evaluated in NP rats, the inhibitory effect of L-NAME on the gastric emptying of the beads was not prevented by L-arginine nor mimicked by L–NMMA. Electrical field stimulation in NANC conditions induced frequency-dependent relaxations in the fundus strips and relaxations followed by rebound contractions in the pyloric strips. These electrically induced NANC relaxations and their reduction by 3×10–4 M L-NAME were not different between NP and P20 rats. It can be concluded that no evidence for a regulatory role of NO in the gastric emptying of the beads was found, and that the nitrergic contribution to the gastric emptying of liquids and to the fundic and pyloric NANC relaxations was not influenced by pregnancy in rats.
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  • 45
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    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 701-704 
    ISSN: 1432-1912
    Keywords: Key words Oxytocin ; Rat ; Musculocutaneous flap ; Wound healing ; Oxytocin antagonist ; Growth factors ; IGF-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to evaluate the effect of oxytocin on survival of musculocutaneous flaps in male Sprague-Dawley rats. For this purpose oxytocin (0.1 or 1.0 mg/kg), an oxytocin antagonist (1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin) (1.0 mg/kg) alone or in combination with oxytocin (1.0 mg/kg) or saline was given subcutaneously (s.c.), 24 hours and 1 hour before and 24 hours after flap surgery. In addition, oxytocin (1 µg/kg) or saline was given intracerebroventricularly (i.c.v.) according to the same schedule. Six days after surgery the amount of viable tissue was measured. Oxytocin 1.0 (but not 0.1) mg/kg s.c. and 1.0 µg/kg i.c.v. increased survival of the flaps (s.c.: 13.8±14.6% versus 6.10±5.45%; p〈0.05 and i.c.v.: 25.5±14.0% versus 10.3±5.79%; p〈0.01). This effect was abolished by the oxytocin antagonist. Furthermore, the oxytocin-treated rats had significantly higher plasma levels of insulin-like growth factor-1 (IGF-1) (p〈0.05). These data indicate that oxytocin increases the survival of musculocutaneous flaps. The effect seems to be exerted within the central nervous system since a 1000 fold lower dose of oxytocin given i.c.v. increased flap survival to the same extent as the s.c. given dose. IGF-1 might be one of the mediators of this effect.
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  • 46
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    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 413-418 
    ISSN: 1432-1912
    Keywords: Key words PBR ; Kainate ; Reactive oxygen species ; Glutamate ; U-83836E ; Mitochondria ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%±35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10–9 to 5×10–6M) completely inhibited this increase, with an IC50 value of 3.02±1.08×10–7M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1±0.8μM. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicityin vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the Bmax to 1341±192fmol mg–1. When U-83836E was coadministered with KA, the Bmax was reduced to 765±122fmol mg–1, which was not significantly different from the Bmax obtained from untreated rats (Bmax: 518±33fmol mg–1). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.
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  • 47
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Adrenals ; Addisonian crises ; Rat ; Adrenocorticotropic hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigates whether fetal adrenal transplants into the omentum of adrenalectomized rats will be integrated into the recipient's endocrine system to provide competent adrenocortical function. The results demonstrate that fetal adrenals graft with a rich vascular supply, mature histologically, and produce increasing levels of corticosterone. When bilateral adrenalectomy is performed in the recipient, survival is prolonged and addisonian crisis can be prevented. Moreover, adrenocorticotrophic hormone levels decrease with increasing levels of corticosterone, indicating that the fetal grafts are integrated into the physiological pituitary-adrenocortical feedback system.
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  • 48
    ISSN: 1434-0879
    Keywords: Key words Testicular function ; Smoking ; Fertility ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effects of smoking on testicular function and fertilizing potential in rats. Twenty rats (group A) were exposed to the smoke of 20 cigarettes for 1 h per day. Ten rats (group B) were exposed to the smoke of 40 incense sticks for 1 h per day, and an additional 10 rats served as a control group (group C). After 10 weeks of daily exposure, serum levels of nicotine and cotinine were assessed, and a mating test was conducted. Five days later, serum concentrations of testosterone before and after human chorionic gonadotropin (hCG) stimulation, gonadotropins, and epididymal sperm content and motility were evaluated. In addition, in vitro fertilization was carried out. Nicotine and cotinine were detected in group A, but not in groups B and C. Basal serum testosterone and gonadotropin concentrations did not differ significantly among the three groups, but the testosterone response to hCG stimulation was significantly lower in group A than in groups B and C. Group A showed significant reductions in epididymal sperm content and motility, and in fertility in vivo and in vitro. These findings suggest that smoking leads to a secretory dysfunction of the Leydig cells, and also a deficiency in sperm maturation and spermatogenesis. In addition, smoking has a detrimental effect on sperm fertilizing potentials in vivo and in vitro.
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  • 49
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    Urological research 26 (1998), S. 325-330 
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Obstruction ; Hypertrophy ; Cystometry ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The urodynamic effects of an experimental, partial infravesical outlet obstruction in rats were studied and compared with the effects in sham-operated controls, and in animals that had undergone 24 h of total outlet obstruction. The animals were studied up to 42 days after surgery. Bladder weight increased with time in the partially obstructed group to reach a final value of 6 times that of the control. In water loading experiments micturition volume was unaffected by sham operation. In the partially obstructed bladders it decreased initially but normalized with time. In the group that had undergone 24 h of total obstruction micturition volume also decreased initially but then became significantly higher than in the controls. In cystometry experiments the partially obstructed bladders developed a considerable residual urine and increased threshold and micturition pressures. Detrusor instability was present already after 10 days. Also in the cystometry experiments the bladders that had been totally obstructed for 24 h had increased micturition volumes. Residual volume was only slightly affected by atropine in the control and partially obstructed bladders but increased 7-fold in rats in which the bladder had been totally obstructed for 24 h 42 days previously. We conclude that there is a close relationship between bladder weight, residual volume and micturition pressure in the partially obstructed bladder, and that 24 h of total obstruction results in disturbances of bladder function that might be related to denervation phenomena previously reported by others.
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  • 50
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    Urological research 26 (1998), S. 291-297 
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Rat ; Pelvic ganglion ; Innervation ; Denervation ; Plasticity ; Age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the degree of neuronal plasticity following a partial denervation of the rat urinary bladder. Using acetylcholinesterase staining we found that the postganglionic nerves from the pelvic ganglion reach the intact bladder as 1–4 nerve trunks on each side, slightly ventral and caudal to the ureteral orifices. Normally a few thinner nerves also reach the bladder posterolateral to the ureterovesical junction. The nerves ventral to the ureters run in the ventral longitudinal muscle layer as well-defined trunks with a pattern that does not differ much from one animal to another. The nerves reaching the bladder dorsolaterally innervate the dorsolateral aspects in a more irregular fashion. Some anastomoses are found across the midline between nerves from either side. This nerve pattern is already in place in newborn rats. After removal of the pelvic ganglion on one side in the adult rat the ipsilateral ventral nerves rapidly degenerate, whereas some dorsolateral␣nerves usually survive. Axons from the intact ventral␣nerves can be seen crossing over to the denervated side in the anastomoses. After 13 weeks the surviving ventral nerves, which normally run at some distance from the ventral midline, now run in the midline with equal amounts of ventral longitudinal muscle on either side, and with their branches evenly distributed to both sides. The same pattern is seen after 27 weeks. Unilateral ganglionectomy in 3-week-old rats leads to the same changes in nerve distribution as in the adult rat. We conclude that there is a high degree of plasticity in the bladder innervation following a partial denervation, and that this plasticity includes the distribution of its main intramural nerve trunks.
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  • 51
    ISSN: 1432-0533
    Keywords: Key words Endothelial barrier antigen ; Blood-brain ; barrier ; Immunohistochemistry ; Rat ; Spinal cord
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The endothelial barrier antigen (EBA) recognised by a monoclonal antibody is expressed in rat cerebral microvessels possessing blood-brain barrier properties but only weakly by fenestrated vessels. We have studied the expression of this marker in the spinal cord of control rats and compared the findings with those seen in rats subjected to compression injury at the T8–9 level with a survival period of 4 h, 24 h, 4 days and 9 days. To that end, formalin-fixed paraffin-embedded material was immunostained by the avidin-biotin-peroxidase complex method. Sections from control rats presented a distinct immunostaining at the site of the endothelial cells of almost all microvessels in the grey and white matter of the cord. The anterior and posterior spinal arteries did not show such staining. Neurons and glial cells were unstained. Rats which had survived 4 h after a moderate or severe compression trauma still showed immunoreactivity in intramedullary microvessels at the site of injury. There was a moderate reduction of vascular immunoreactivity at 24 h and a pronounced loss of such reactivity at 4 days after trauma. At 9 days after compression the expression of the endothelial barrier antigen had almost been normalised in the microvessels of the cord. In conclusion, using immunohistochemistry, EBA can be demonstrated in noninjured rat spinal cord microvessels, while the staining disappears at the site of compression trauma to the cord. The EBA marker can be used to indicate sites of vascular injury in spinal cord compression injury. The factors causing the disappearance and restitution of the antigen are unknown.
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  • 52
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    Anatomy and embryology 198 (1998), S. 331-339 
    ISSN: 1432-0568
    Keywords: Key words Accessory olfactory bulb ; Vomeronasal epithelium ; Vomeronasal nerves ; Glycoproteins ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A number of previous studies have indicated that lectin histochemistry is an obvious choice for characterizing the vomeronasal system. However, apparently inconsistent results have been obtained: notably, the affinity with which various lectins bind to the accessory olfactory bulb varies among taxa, even considering closely related species. In the present study, the binding patterns of seven lectins in the rat accessory olfactory bulb, vomeronasal nerves and vomeronasal duct were investigated. The Bandeiraea simplicifolia lectin bound exclusively to the vomeronasal nerve and glomerular layers of the accessory olfactory bulb, while the Ulex europeus and Lycopersicon esculentum lectins bound to these regions and additionally to the nerve and glomerular layers of the main olfactory bulb. Soybean agglutinin showed a similar pattern to that obtained with the Ulex europeus and Lycopersicon esculentum lectins, though it also faintly labelled other parts of the structures examined. The Vicia villosa and Erythrina cristagalli lectins were not specific for the vomeronasal system, since they labelled grey and white matters in structures including the lateral olfactory tract and the anterior olfactory nuclei. The Dolichos biflorus lectin did not bind to vomeronasal tissues. The observed patterns of binding in the accessory olfactory bulb were consistent with those observed in the vomeronasal nerves, but unlike those observed in the epithelium of the vomeronasal duct. This latter result probably reflects binding of lectins to sugar residues contained in secreted mucus rather than those in epithelial nerve endings.
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  • 53
    ISSN: 1432-0568
    Keywords: Key words Pituitary adenylate cyclase-activating peptide (PACAP) ; Small intestine ; Large intestine ; Enteric nervous system ; Rat ; Immunohistochemistry ; Synapse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pituitary adenylate cyclase-activating peptide (PACAP)-immunoreactive (IR) neurons in the myenteric and submucosal plexus of the rat small and large intestine were examined by immunostaining with purified polyclonal antiserum against PACAP (1–15), using both light and electron microscopy. Many PACAP-IR neuronal cell bodies and fibers were found in the myenteric and submucosal plexus. Many of the PACAP-IR fibers originated from the cell bodies of the myenteric and submucosal ganglia. The ganglia were also innervated by PACAP-IR fibers. PACAP-IR fibers penetrated both the circular and longitudinal muscle layers, confirming the previous observations indicating that PACAP neurons act as motor neurons. Ultrastructural study demonstrated that PACAP-IR nerve terminals formed synaptic contacts with PACAP-IR nerve cell bodies or dendritic processes. This observation suggests that PACAP-IR neurons innervate other PACAP-IR neurons, and that PACAP neurons work as interneurons in the enteric nervous system. PACAP-IR nerve cells received not only PACAP-positive nerve terminal input also PACAP-negative nerve terminal input. It also suggests that PACAP neurons are regulated not only by PACAP-IR enteric neurons, but also by neurons originating elsewhere. Our observations support the view that PACAP-IR neurons are involved in the control of gut motility.
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  • 54
    ISSN: 1432-0533
    Keywords: Key words Glucose ; Selective vulnerability ; Isolectin ; Glial fibrillary acidic protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We undertook a detailed characterization of the cellular responses to acute global cerebral ischemia complicated by hyperglycemia. Anesthetized, physiologically monitored male Wistar rats received 12.5 min of global forebrain ischemia by bilateral common carotid artery occlusions plus hemorrhagic hypotension to 45 mm Hg. Cranial temperature was maintained at normothermic levels. Hyperglycemic animals received dextrose (2.5 ml of a 25% solution, intraperitoneally) prior to ischemia; this doubled the mean plasma glucose concentration to 296 mg/100 ml. At 3 days (n = 10) or 24 h (n = 4) after ischemia, brains were perfusion-fixed and paraffin-embedded for light microscopic histopathology and for the histochemical visualization of activated microglia and the immunocytochemical visualization of glial fibrillary acid protein. Normal-neuron counts in the vulnerable hippocampal CA1 sector of hyperglycemic-ischemic (HI) rats were reduced to one-third the number observed in normoglycemic-ischemic (NI) animals. Ischemic cell counts in the striatum were increased fivefold or more in HI compared to NI rats, and normal small-neuron counts were reduced by two-thirds. The neocortex and striatum of NI rats showed only mild damage, while the majority of HI rats had extensive lesions, and several showed large cortical, striatal or thalamic infarcts. In addition, widespread cortical ischemic neuronal changes were evident in HI animals. No endothelial alterations were present in NI rats. By contrast, HI rats showed prominent peri- and intravascular polymorphonuclear and monocytic accumulation evident at 24 h; frequent white cell thrombi in pial arterioles on day 3; and thickening of vascular endothelium, with foci of parenchymal rarefaction or microinfarction adjacent to occluded vessels. Prominent microglial activation, often along the course of penetrating blood vessels, was common in the striatum and neocortex of HI animals but was much less extensive in the NI group. Activated microglia in HI rats were typically hypertrophic and amoeboid. These results suggest that the detrimental influence of hyperglycemia in ischemia is initially mediated by an action on vascular endothelium, which in turn leads to widespread foci of infarction and neuronal loss.
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  • 55
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    Acta neuropathologica 96 (1998), S. 351-356 
    ISSN: 1432-0533
    Keywords: Key words Apoptosis ; Hyperthermia ; Glioma ; Rat ; c-Jun
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hyperthermia has been shown to inhibit glioma growth both in vitro and in vivo, and has been reported to induce apoptosis of a variety of cells. We investigated the role of apoptosis in tumor cell death following hyperthermia in a rat glioma model representing human glioblastoma. Apoptotic cell death was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and hematoxylin and eosin (H & E) staining. We also examined c-Jun expression immunohistochemically. Apoptotic cell death in rat brain tumors that grew after implantation of C6 glioma cells showed regional differences. In all rats, apoptotic cells, characterized by extreme chromatin condensation and fragmented nuclei with apoptotic bodies in H & E-stained sections, were observed in the gliomas’ necrotic cores. TUNEL-positive cells were observed in the border zones between necrotic and vital tumor cells. Before hyperthermia, TUNEL-positive cells were sporadically distributed in the vital tumor tissue. After hyperthermia, the number of TUNEL-positive cells in the peripheral region of the tumor mass increased significantly, reached a peak after 6 h and returned to the basal level within 24 h (P 〈 0.01). C-Jun protein immunoreactivity was not observed in the cells at the tumor periphery. These data indicate that significantly apoptotic cell death unrelated to c-Jun expression occurs after hyperthermia, and that this form of cell death may be the mechanism of tumor regression following hyperthermia treatment of intracranial gliomas.
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  • 56
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    Anatomy and embryology 198 (1998), S. 53-61 
    ISSN: 1432-0568
    Keywords: Key words Regenerating spermatogonia ; Asymmetric divisions ; Cytoplasmic bridges ; Busulfan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study describes the morphological behaviour of spermatogonia following recovery from two doses of busulfan treatment in the rat. Twenty days after the second intraperitoneal injection of busulfan, the testes lost most of their spermatogenic cells and there were fewer dispersed singly surviving spermatogonia. These surviving cells were in close contact with the basal portions of adjacent Sertoli cells and the shrunken basal lamina, and were the source for repopulating the depleted seminiferous epithelium. During the initial stage of repopulation (48 days later), surviving spermatogonia underwent a phase of active proliferation: type A spermatogonia underwent symmetric and asymmetric divisions; type B spermatogonia underwent asynchronous differentiation. At day 96, normal spermatogenesis was fully recovered in many seminiferous tubules, represented by 80% of the rats regaining various degrees of fertility at day 120. These data provide an additional model for the study of self-renewal of stem spermatogonia and suggest that the asymmetric division of type A spermatogonia and their close contact with both the basal lamina and the Sertoli cells may be involved in regulating the number of stem spermatogonia and the delicate process of normal spermatogenesis.
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  • 57
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    Acta neuropathologica 96 (1998), S. 151-156 
    ISSN: 1432-0533
    Keywords: Key words Neuropathy ; Hypoglycemia ; Insulin ; implant ; Rat ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-dependent diabetes mellitus is a chronic metabolic disease that causes long-term secondary complications such as neuropathy. The occurrence of diabetic neuropathy has generally been thought of as being associated with hyperglycaemia. However, in a previous light microscopic examination of plantar nerves in diabetic BB/Wor rats treated with insulin implants we found that eu-/hyperglycaemic rats present a normal picture, whereas eu-/hypoglycaemic rats show severe changes. The aim of the present work is to supplement our previous light microscopic report with electron microsocpic data from the lateral plantar nerve of normal, eu-/hyperglycaemic and eu-/hypoglycaemic BB/Wor rats. Under the electron microscope lateral plantar nerves collected from eu-/hyperglycaemic rats presented a qualitatively normal picture. In addition, the fibre numbers and the size distribution of the myelinated fibres were normal. In contrast, specimens from eu-/hypoglycaemic BB/Wor rats showed severe qualitative changes, interpreted as signs of axonal de- and regeneration. The total number of axons was somewhat subnormal and the sizes of the myelinated fibres were strongly shifted towards smaller diameters. These data confirm our previous light microscopic observations. We conclude that eu-/hypoglycaemic BB/Wor rats treated with insulin implants, but not similarly treated eu-/hyperglycaemic animals, develop a neuropathy in their plantar nerves.
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  • 58
    ISSN: 1432-0568
    Keywords: Key words Claustrum ; Visual cortex ; Visual zones Comparative anatomy ; Rat ; Guinea pig ; Rabbit ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The retrograde axonal transport method was used to compare the topography and organization of the visual zone of the claustrum in rat, guinea pig, rabbit and cat. First, massive Fluoro-Gold injections were placed into the primary visual cortex and the secondary areas. Experiments showed differences in the location of the visual zone among the animals under study. In rat, the visual zone occupied the posteroventral part of the claustrum and spread to its anterior pole. In guinea pig, neurons projecting to the visual cortex were located dorsally in the posterior half of the claustrum. In rabbit, similarly to the rat, they were localized in the posteroventral part; however, they did not reach the anterior pole. In cat, neurons that project to the visual cortex were concentrated dorsally in the posterior fourth of the claustrum. In double-injection experiments, Fast Blue and Diamidino Yellow were placed into the primary and secondary visual areas in various combinations. The experiments showed that in the rat and the rabbit claustral neurons project to primary visual cortex (area 17) as well as to both secondary visual areas (areas 18a and b). Populations of neurons sending axons to the primary and secondary areas showed full overlap. The presence of double-labeled neurons indicates that some claustral neurons project both to the primary and secondary fields. In cat, neurons that project to the primary visual cortex appear to be clearly separated from those connected with the secondary visual area, as no double-labeled neurons were found. In all studied species, the double injections placed into the visual and primary somatosensory cortex did not result in any double-labeling neurons. Our results indicate that the location of the visual zone in the posterior part of the claustrum is a phylogenetically stable feature, whereas its dorsoventral shift as well as the extent toward the anterior pole is related to the particular species. The overlap of neurons projecting to the primary and secondary visual areas in the rat and rabbit as well as the separation of both projections in cat appear to reflect the higher degree of complexity of the visual system in the latter.
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  • 59
    ISSN: 1432-0533
    Keywords: Key words Focal ischemia ; Protein synthesis ; Substantia nigra ; Thalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Following focal cerebral ischemia, neuronal cell death is detected in remote areas of the brain, including the ipsilateral thalamus and substantia nigra (SN), as well as in the ischemic core. We have investigated protein synthesis in the remote areas of rats exposed to focal ischemia using autoradiography. The proximal portion of the left middle cerebral artery (MCA) was permanently occluded, and at various periods (6 h, 2, 4 and 7 days and 2 and 4 weeks following ischemia) animals received a single dose of l-[2,3-3H]valine (6.7 mCi/kg). Brain sections containing the thalamus and SN were processed for autoradiography. In the ipsilateral cerebral cortex and striatum, marked impairment of protein synthesis was observed and was never completely recovered during the experiment. No changes in protein synthesis in the ipsilateral thalamus were detected during the experiment. However, a change in protein synthesis was demonstrated in the ipsilateral SN. At 2 days after MCA occlusion, incorporation of [3H]valine into the whole zona reticulata of the ipsilateral SN was slightly enhanced and the increase became evident at 4 days after ischemia. Increased incorporation of [3H]valine began to be localized in the lateral portion of the zona reticulata after 7 days and continued up to 4 weeks following ischemia. Enhanced protein synthesis during the early stage (2 and 4 days after ischemia) may be due to the activated function of the neurons in the zona reticulata and that during the late stage (7 days and 2 and 4 weeks) after ischemia to astroglial proliferation
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  • 60
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    Anatomy and embryology 197 (1998), S. 439-450 
    ISSN: 1432-0568
    Keywords: Key words Meckel’s cartilage ; Chondrocyte ; Transformation ; Resorption ; Apoptosis ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is unknown whether cells in the midportion of Meckel’s cartilage undergo transformation into other kinds of cell or whether resorption of cells occurs during development. Therefore, the midportion of Meckel’s cartilage from the mouse and the rat was subdivided into anterior and posterior portions. The ultimate fates of these tissues were analyzed with a focus on resorption-related cells, death of chondrocytes by apoptosis, and transformation of the chondrocytes themselves. Cellular and extracellular features of mouse Meckel’s cartilage were observed after von Kossa’s staining and staining for acid phosphatase (APase) activity, as well as by light and electron microscopy. To identify resorbing cells, immunostaining specific for macrophages and staining for tartrate-resistant acid phosphatase (TRAP) were performed. The DNA nick end-labeling (TUNEL) method was used for the detection of death of chondrocytes by apoptosis. The replacement of the extracellular matrix of rat Meckel’s cartilage was examined with double immunofluorescence staining for type I and type II collagens. When the anterior midportion from embryonic mice on day 18 was examined after von Kossa’s staining, it was clear that the extracellular matrix had already calcified and vascularization had been initiated that reflected the calcified matrix. TRAP staining and immunostaining for macrophages revealed two types of osteoclast and macrophages that were involved in resorption of the matrix. In the posterior midportion, no vascular invasion was evident, and chondrocytes were transformed directly into fibroblastic cells by phenotypic conversion. In such cells we found reaction products specific for APase activity, suggestive of the intracellular degradation of fine collagenous fibrils. Double immunofluorescence staining showed that cartilage-specific type II collagen was replaced by type I collagen with the phenotypic transformation to fibroblastic cells. There were no significant changes in the number of TUNEL-positive apoptotic cells from day 17 of gestation to day 6 after parturition. Death of chondrocytes by apoptosis was not, therefore, involved directly in the disappearance of Meckel’s cartilage. These results in the posterior midportion served as an instance of phenotypic switches in differentiated cells from chondrocytes to fibroblast-like cells. The present study indicates that there is a difference between the ultimate fate of cells in the posterior part and that of cells in the anterior part in the midportion of Meckel’s cartilage in the mouse and rat.
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 206 (1998), S. 393-398 
    ISSN: 1431-4630
    Keywords: Key words Dietary fibre ; Sugar beet pulp ; Biochemical parameters ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Groups of 15 male rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5.0 or 10.0% dietary fibre (DF) prepared from sugar beet. The highest food consumption was found in the group with 10% DF in the diet. Food efficiency was highest in the control group. Average body weight increased continuously in all groups without significant differences. Enrichment of the diet with the DF preparation did not substantially influence urinary parameters [pH, specific gravity, protein or activities of aspartate aminotransferase (ASAT), alanine aminopeptidase and alkaline phosphatase (AP)]. Haemoglobin concentration and haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular volume as well as total numbers of erythrocytes, thrombocytes and leukocytes counts did not significantly differ between the groups. Lower counts of eosinophils and neutrophils were measured in rats fed DF-enriched diets. Serum parameters (urea-N, protein, glucose, triglycerides and activities of ASAT, alanine aminotransferase, AP and leucine aminopeptidase) did not differ between groups. As the amount of DF preparation in the diet increased, serum cholesterol was reduced in trend. Furthermore, no significant differences were found between the groups with respect to the organ weights of rats. In conclusion, important or critical dose-related differences in the determined parameters were not found. This sub-acute feeding study showed that no toxic effects were related to used doses of DF which was prepared from sugar beet.
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  • 62
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    Zeitschrift für Lebensmittel-Untersuchung und -Forschung 207 (1998), S. 66-73 
    ISSN: 1431-4630
    Keywords: Key words Dietary fibre ; Sugar beet pulp ; Composition ; Fermentation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract  Groups of 15 female rats were fed ad libitum for 4 weeks with a standard diet containing 0, 2.5, 5 or 10% of a dietary fibre (DF) preparation made on a laboratory scale from sugar beet pulp. This preparation had a total DF content of 72.2%. Its major components were 36.7% cellulose, 16.9% pectin, 16.8% hemicelluloses (HC) and 11.0% protein. The DF preparation from sugar beet exhibited a water-binding capacity (WBC) of 8.9 g H2O/g. As the proportion of DF preparation in the diet increased, up to 15.8% total DF, 4.6% cellulose and 1.9% pectin were found in the feeds. The WBC of the diets was estimated to be 1.4–2.9 g H2O/g. At the end of the experiment, 20.3–64.1% total DF, 10.3–38.2% cellulose, 0.2–7.8% pectin, 4.3–9.2% HC pentoses and 4.3–10.3% HC hexoses were determined in caecum contents (ca. 0.6 g dry weight/rat). The following proportions were found in faeces (3rd week; 1.4–1.9 g dry weight/rat): 34.5–56.9% total DF, 19.5–36.1% cellulose, 6.4–8.4% HC pentoses, 7.4–8.3% HC hexoses. The WBC of faeces ranged from 3.7 g H2O/g to 4.9 g H2O/g. About 30–50% of the daily intake of DF appeared in the faeces. Higher amounts of total DF, pectin and HC pentoses were fermented by gastrointestinal microflora as the concentration of DF preparation from sugar beet in the diet increased. In addition, the fermentation of different DF components could be shown by the monosaccharide composition of caecum contents and faeces.
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  • 63
    ISSN: 1432-1211
    Keywords: Key words CD1 ; Rat ; Gene ; Organization ; Polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5′ flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5′ region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.
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  • 64
    ISSN: 1432-1211
    Keywords: Key words RT1.S3 ; Grc ; MHC ; Class I ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
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  • 65
    ISSN: 1432-1238
    Keywords: Key wordsK. pneumoniae ; Bacteremia ; Mechanical ventilation ; Blood gases ; Animal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine the effect of peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) on the development of bacteremia with Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated rats. Design: Prospective, randomized, animal study. Setting: Experimental intensive care unit of a University. Subjects: Eighty male Sprague Dawley rats. Interventions: Intratracheal inoculation with 100 μl of saline containing 3.5–5.0 × 105 colony forming units (CFUs) K. pneumoniae/ml. Pressure-controlled ventilation (frequency 30 bpm; I/E ratio = 1 : 2; FIO2 = 1.0) for 180 min at the following settings (PIP/PEEP in cmH2O): 13/3 (n = 16); 13/0 (n = 16); 30/10 (n = 16) and 30/0 (n = 16), starting 22 h after inoculation. Arterial blood samples were obtained and cultured before and 180 min after mechanical ventilation and immediately before sacrifice in two groups of non-ventilated control animals (n = 8 per group). After sacrifice, the lungs were homogenized to determine the number of CFUs K. pneumoniae. Measurements and results: The number of CFUs recovered from the lungs was comparable in all experimental groups. After 180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/0, whereas only 2, 0 and 2 animals were positive in 13/3, 13/0 and 30/10, respectively (p 〈 0.05 group 30/0 versus all other groups). Conclusions: These data show that 3 h of mechanical ventilation with a PIP of 30 cmH2O without PEEP in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH2O PEEP at such PIP reduces ventilation-induced K. pneumoniae bacteremia.
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  • 66
    ISSN: 1432-1335
    Keywords: Key words Small-intestine phenotype ; Sucrase ; Intestinal-type alkaline phosphatase ; Colon cancer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.
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  • 67
    ISSN: 1432-1106
    Keywords: Key words Central pain ; Endogenous opioids ; Naloxone ; Neuropathic pain ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and nonallodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of μ and δ opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective κ-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal κ-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal μ and δ, but not κ, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal pain-related behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.
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  • 68
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    Experimental brain research 118 (1998), S. 361-372 
    ISSN: 1432-1106
    Keywords: Key words Noradrenaline ; Neuromodulator ; Iontophoresis ; Intensity function ; Threshold ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To test a potential “gating” effect of noradrenaline (NA) in the auditory cortex, the acoustic threshold was estimated by determining the rate-level function of neurons before, during, and after microiontophoretic application (5–40 nA) of NA. The rationale behind this experiment was that a gating effect should decrease the threshold for acoustic excitatory responses. From 84 recorded neurons, we observed (1) that application of NA increased the threshold for 48 of 84 cells, and (2) that, on average, the slope of the rate-level functions was unchanged. These effects on the threshold are consistent with the fact that the dominant effect of NA on the evoked response is inhibition for 34 of 84 cells; increases in evoked responses were observed for only 14 of 84 cells. GABA application (0–50 nA) also led to increased response threshold for 19 of 24 cells (unaffected, 5 of 24 cells). However, for three cells the effect of GABA application was antagonized by bicuculline application, while on the same cells bicuculline application did not prevent the noradrenergic increase in threshold. The effect induced by NA on the threshold raises questions about the generality of a gating effect of NA in sensory neocortex.
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  • 69
    ISSN: 1432-1106
    Keywords: Key words Posterior hypothalamus ; Histamine ; Memory ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tuberomammillary nucleus (TM) located in the posterior part of the hypothalamus is the main source of neuronal histamine in the central nervous system. Recent work from our laboratories has indicated an involvement of the TM region in neuronal plasticity and reinforcement processes. In the present study, we investigated the effects of TM lesions on the performance of adult and aged Wistar rats in a set of learning tasks, which differed in terms of complexity and reward contingencies (habituation learning, inhibitory avoidance, discrimination learning, Morris water maze). An improvement was found in every test applied, indicating that TM lesions seem to generally enhance learning and memory capacities independent of the special demands of a given task. Age-related learning deficits were strongly diminished. Immunohistochemistry revealed that the excitotoxic lesions used to destroy the TM region led to a marked decrease in the number of histamine-positive neurons in the vicinity of the injection site, indicating an involvement of the brain histaminergic system in the observed behavioral changes.
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  • 70
    ISSN: 1432-1106
    Keywords: Key words Extracellular recording ; Cortical efferents ; A10 cell group ; Non-dopaminergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is rapidly becoming apparent that the prefrontal cortex (PFC) plays a major role in controlling the activity of midbrain dopaminergic (DA) neurons. We have previously demonstrated that electrical stimulation of the PFC elicits inhibition-excitation (IE) and excitation (E) activity patterns in DA neurons in the ventral tegmental area (VTA; A10 cell group). Since non-DA neurons in the VTA are cortically innervated, synapse upon DA neurons and appear to have an inhibitory impact, we determined the extent to which the responses of these neurons to stimulation of the PFC could account for the responses seen in DA neurons upon cortical stimulation. Stimulation of the PFC (0.25 mA and 1.0 mA) elicited three categories of response in the majority of VTA non-DA neurons. Types I and II were characterised by a short-to-moderate latency excitation (referred to as “early excitations”), in the latter case preceded by inhibition. Type III responses consisted of inhibition in the absence of an early excitation. Elements of these responses were compared with the temporal characteristics of key elements of responses elicited in DA neurons by PFC stimulation. Although the early excitations in non-DA neurons preceded the inhibitions in DA neurons exhibiting IE responses, the early excitations began approximately 100 ms before the inhibitions in DA neurons and often ended several tens of milliseconds before the inhibitions began, making a causal relationship between these events unlikely. The inhibitions in Type III responses, combined with the inhibitions which followed the early excitations in many Type I and II responses, showed temporal characteristics that suggested a possible causal relationship with the excitations in DA neurons exhibiting E responses, but not those exhibiting IE responses. However, since the excitatory phases of E and IE responses appear to be homologous, the lack of involvement of non-DA neurons in the excitatory phase of IE responses tends to cast doubt on the involvement of non-DA neurons in the excitation during E responses. In fact, the most coherent impression that emerges is that non-DA neurons in the VTA do not influence the activity of A10 DA neurons on a short time-scale (i.e. phasically), but instead may influence activity on a longer time-scale (i.e. tonically).
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  • 71
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    Experimental brain research 118 (1998), S. 477-488 
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Strength-duration relations ; Conduction velocity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular electrical stimulation of the gray matter is often used to determine the function of a given cortical area or pathway. However, when it is used to elicit postsynaptic effects, the presynaptic neuronal elements activated by electrical stimulation have never been clearly identified: it could be the excitable dendrites, the cell body, the axon initial segment, or the axonal branches. To identify these elements, we performed two series of experiments on slices of rat visual cortex maintained in vitro. The first series of experiments, reported in this paper, was aimed at determining the chronaxie, a temporal parameter related to the membrane properties of the neuronal elements. In order to identify the presynaptic elements that were activated by extracellular electrical stimulation, chronaxies corresponding to postsynaptic responses were measured and compared with those corresponding to the activation of axons (antidromic activation) and those corresponding to the activation of cell bodies (intracellular current injection in intracellularly recorded neurons). The chronaxie for orthodromic activation was similar to that for axonal activation, but was 40 times smaller than the chronaxie for direct cell body activation. This suggests that, whenever a postsynaptic response is elicited after electrical stimulation of the cortical gray matter, axons (either axonal branches or axon initial segments), but not cell bodies, are the neuronal elements activated.
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  • 72
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Intracortical microstimulation ; NMDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-d-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15—20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimualtion.
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  • 73
    ISSN: 1432-1106
    Keywords: Key words Thalamic reticular nucleus ; Learning ; Memory ; Two-way active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments were performed in order to study the effects of lesions of the rostral thalamic reticular nucleus (Rt) on two-way active avoidance. Male wistar rats were subjected to either a bilateral electrolytical lesion of the rostral Rt or to control procedures. After recovery, all rats were trained in either a distributed (five training sessions, ten trials each; experiment I) or a massed (a single 30-trials session; experiment II) two-way, active-avoidance task. The level of long-term retention of the task was assessed 10 days later. Lesioned rats showed an overall higher performance than control rats both in experiment I (with lesions affecting the rostral Rt and small portions of some adjacent nuclei) and in experiment II (with lesions almost restricted to the rostral Rt). In contrast, detrimental effects on other tasks have been reported in the literature. Although it cannot be ruled out that those differences might be due to methodological factors, they also might be indicative of an action of rostral Rt lesions on certain mechanisms (either indirectly or directly related to information processing) that could be differentially required depending on the kind of learning task. The latter possibility is discussed in terms of the role played by this nucleus as a modulator of thalamocortical transmission, attentional mechanisms and cortical arousal.
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  • 74
    ISSN: 1432-1106
    Keywords: Key words Dextromethorphan ; Tirilazad mesylate ; Combination drug therapy ; Cerebral ischemia ; Cerebral blood flow ; Neuroprotection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cell death after cerebral ischemia is mediated by a massive release of excitatory amino acids, generation of free radicals, and – a crucial step – calcium influx into cells. We examined the hypothesis that concurrent administration of drugs ameliorating brain damage via different mechanisms would result in a synergistic neuroprotective effect. The neuroprotective efficacy of two clinically available drugs – the N-methyl-d-aspartate and calcium-channel antagonist dextromethorphan (DM) and the antioxidant tirilazad – were studied in monotherapy and in combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal filament technique. The animals were randomly assigned to one of four treatments (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4) DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by continuous laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed planimetrically after 7 days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF. Monotherapy with DM or tirilazad improved neurological function and reduced infarct volume by 45% and 48%, respectively. Combination therapy failed to influence neurological recovery and infarct volume. Although, from pharmacological point of view, a synergistic neuroprotective effect is expected, combination of dextromethorphan and tirilazad may lead to mutual inhibition or potentiate adverse effects.
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  • 75
    ISSN: 1432-1106
    Keywords: Key words Urinary bladder ; Inflammation ; Nucleus centralis of amygdala ; Bed nucleus of the stria terminalis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This article is the fifth of a series aimed at mapping brain activities as they result from the development of cyclophosphamide (CP) cystitis in behaving rats using c-fos and Krox-24 expression. The inactive hepatic metabolites of CP are metabolized in the kidney to produce acrolein, which generates cystitis. Data come from animals which were injected once i.p. with either 1 ml saline (sham) or 100 mg/kg CP in 1 ml saline under transient volatile anesthesia and which behaved freely for 1–4 h postinjection, 4 h being the minimum time for cystitis to completely develop. Survival times longer than 4 h were not studied owing to ethical considerations. The first 2 h postinjection cover a period of time over which inputs of multifactorial origin (stress and pain due to the intraperitoneal injection process, possible effects due to the presence of hepatic CP metabolites in blood, cystitis onset) interact in an indistinguishable way; the last 2 h are more cystitis specific as the other effects have vanished. Complete screening of telencephalic levels has been performed. These data complete previously published data at both spinal and subtelencephalic levels. Of all the telencephalic structures, only the bed nucleus of the stria terminalis in the dorsal part of its lateral division (BSTLd) and, to a lesser degree, the nucleus centralis of the amygdala, mostly in its caudal portion (cCeA), appeared to be significantly driven over the most specific cystitis period. Both of these structures had related, but not identical patterns of expression. They both reacted shortly after CP injection, but, while cCeA maintained its activity throughout cystitis development, BSTLd showed a rebound, reaching a peak value when cystitis was fully developed. Both of these areas are the only telencephalic areas to contain high PACAP38 immunoreactivity. This is evidence that, (1) both the BSTLd and cCeA could be the most rostral areas that visceronociceptive inflow would reach when cystitis genesis is under way, and (2) PACAP38 could be one of the neurochemical agents involved in telencephalic visceronociceptive processing. From our complete mapping of brain activities under a fully developed cystitis situation (4 h postinjection), it appears that the activities in BSTLd and cCeA are concomittant with those of both the dorsal vagal complex (DVC), paratrigeminal nucleus (PaT), and the ventrocaudal bulbar reticular formation (vcBRF) at brainstem levels, suggesting they all form the main part of the neural network that subserves the central processing of cystitis-related inputs, comprising pain and associated pseudoaffective responses. Both the DVC and BSTLd, which are the most powerfully driven areas, would be particularly important in such a way. The origin of these activities should be found in both vagal (as sensed through PaT activity) and spinal (pelvic) influences. This network profoundly differs from those reported for painful situations, either somatic or visceral, which controversally accompany positive cardiac inotropism.
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  • 76
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    Experimental brain research 122 (1998), S. 196-202 
    ISSN: 1432-1106
    Keywords: Key words Opioid ; Enkephalin ; Medial vestibular nucleus ; Age ; In vitro ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective μ-, κ- and δ-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the δ-opioid receptor agonists [d-Ala2, d-Leu5]-enkephalin (DADLE) and [d-Pen2, Pen5]-enkephalin (DPLPE). The μ-opioid receptor agonist morphine and the κ-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The δ-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of δ- but not μ- or κ-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60–80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2–3 weeks. This age-dependence may be due to post-natal changes in the density of δ-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.
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  • 77
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    Experimental brain research 119 (1998), S. 166-170 
    ISSN: 1432-1106
    Keywords: Key words Locus coeruleus ; Analgesia ; Inflammation ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We evaluated the effects of systemic administration of a low dose of naloxone in rats with bilateral lesions in the area of the locus coeruleus (LC) under conditions of unilateral inflammation, compared with those in sham-operated rats. In each group, rats received a single s.c. injection of carrageenan (6 mg in 0.15 ml saline), and effects of a low dose of naloxone (5 μg/kg, i.p.) on thermal nociception were examined at 4 h and 7 days following the induction of unilateral hindpaw inflammation. The antinociceptive effect was assessed by prolongation of the paw withdrawal latency (PWL) to noxious thermal stimuli. Prior to induction of inflammation, the low dose of naloxone had no significant effect on PWLs in either the sham-operated or the LC-lesioned rats. Four hours after carrageenan injection, the low dose of naloxone produced prolongation of PWLs in the sham-operated rats but failed to induce antinociception in the LC-lesioned rats. Antinociceptive effects were observed in both groups of rats 7 days after carrageenan injection. These results suggest that the LC is involved in naloxone-induced antinociception during the early phase of inflammation.
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  • 78
    ISSN: 1432-1106
    Keywords: Key words Growth-associated protein-43 ; Galanin ; c-jun ; Low-affinity nerve growth factor receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The axotomy reaction in motoneurons after a peripheral nerve transection in the adult animal is characterized by a robust upregulation of alpha-calcitonin gene-related peptide (CGRP) messenger RNA (mRNA) together with mRNAs encoding cytoskeletal and growth-related proteins. Here we have examined whether the nature of the lesion and the age of the animal have any impact on the mRNA regulation in severed cells. Thus, the effect of a sciatic nerve transection in the adult rat was compared with, on the one hand, ventral root avulsions in the adult animal and, on the other hand, sciatic nerve transection in the immature animal. In the two latter cases, a proportion of the lesioned cells die and overall chances of regeneration are small. In the adult animal a sciatic nerve transection induced an upregulation of alpha-CGRP mRNA from the 3rd day after surgery and throughout the first 3 weeks (the time span of the study). Also low-affinity nerve growth factor receptor (p75) and growth-associated protein-43 (GAP-43) mRNAs were upregulated during the entire 3-week period. In contrast, after ventral root avulsion, the expression of alpha-CGRP, c-jun, and p75 mRNAs were normalized within the 1st postoperative week, while GAP-43 mRNA was still upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became upregulated preferentially in motoneurons subjected to ventral root avulsion, while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter type of injury. In the immature animal, alpha-CGRP mRNA was downregulated after sciatic nerve transection in rats aged 3 days or 7 days at the time of surgery; while, in contrast, an upregulation was seen in 12- or 21-day-old animals. GAP-43 and c-jun mRNAs were upregulated in lesioned motoneurons of all ages, while GMAP mRNA was upregulated preferentially in lesioned motoneurons of early postnatal animals. p75 mRNA was expressed in unlesioned immature motoneurons until the age of 7–10 days. The downregulation of p75 mRNA in intact cells at this age coincided with a developmental switch in the ability of axotomized cells to express increased levels of p75 mRNA. No expression of NOS mRNA was detectable in lesioned cells of any of the age groups. These results show that the age of the animal and the type of axonal injury are indeed to a high degree influencing the changes seen in the protein expression pattern in axotomized rat motoneurons. The different responses in these paradigms suggest differences in the trophic response from surrounding glia or the trophic responsiveness of lesioned motoneurons. Also, the results may indicate different roles for the studied substances during the regenerative response of lesioned neurons. Of the substances studied here, upregulation of alpha-CGRP and p75 mRNAs best correlated with a possibility of axon regeneration.
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  • 79
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    Experimental brain research 120 (1998), S. 193-201 
    ISSN: 1432-1106
    Keywords: Key words EMG ; Motor unit activity ; Partial denervation ; Interlimb coordination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  After partial denervation, the remaining motor units (MUs) of adult fast extensor digitorum longus muscle (EDL) expand their peripheral field. The time course of this event was studied using tension measurement and recordings of electromyographic (EMG) activity. The results show that after section of the L4 spinal nerve, when only 5.3 ± 0.63 of the 40 MUs normally supplying EDL muscle remain, the force of individual motor units starts to increase between the 1st and 2nd week after the operation and continues to do so for a further week. The drastic reduction of the number of motoneurones supplying the fast EDL leads to an increase in activity of the remaining MUs. In the 1st week after partial denervation, there was a sharp increase in the EMG activity of remaining motor units. During the next 12 days, this increase became less marked, but EMG activity remained nevertheless significantly higher than that of the unoperated EDL muscle. Many MUs became tonically active during posture. The EMG activity pattern during locomotion was also altered, so that the burst duration was positively correlated with the step cycle duration. Moreover, shortly after partial denervation, the interlimb coordination was disturbed but returned to its original symmetrical use 1–2 weeks later.
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  • 80
    ISSN: 1432-1106
    Keywords: Key words Basal ganglia ; Hippocampus ; Tectum ; Dopamine ; Serotonin ; Histamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies in the rat have shown that the hypothalamic tuberomammillary nucleus, the major source of neuronal histamine, is related to mechanisms of learning, memory, reinforcement, and functional recovery. These functional relationships were found to be partly lateralized. Therefore, we decided to analyze whether unilateral ibotenic acid lesions aimed at this brain region would acutely lead to asymmetries in open-field behavior, and whether they would affect the biogenic amines dopamine and serotonin in the neostriatum, hippocampus, and tectum. We compared this manipulation with unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta and with unilateral ibotenic acid lesions of the substantia nigra pars reticulata. These lesions were investigated because all three brain areas are anatomically linked to the neostriatum, are related to the neurotransmitters dopamine and serotonin, and play a role in behavioral asymmetry and functional recovery. In support of previous findings, our data show that 6-hydroxydopamine lesions of the substantia nigra pars compacta led to an ipsiversive asymmetry in turning and scanning. Ibotenic acid lesions of the adjacent pars reticulata led to contraversive turning, whereas thigmotactic scanning was reduced bilaterally. In contrast, ibotenic acid lesions of the tuberomammillary nucleus did not affect turning, but led to an ipsilateral asymmetry in scanning. Neurochemically, the 6-hydroxydopamine lesion was mainly characterized by the well-known ipsilateral neostriatal dopamine depletion and increased residual dopamine activity. In hippocampus and tectum, these transmitters were not specifically affected, except for an asymmetry of serotonin in the superior colliculus. The ibotenic acid lesions of the pars reticulata did not deplete neostriatal dopamine, indicating that they spared the dopaminergic output of the substantia nigra. In contrast, they affected dopaminergic and serotonergic measures in the colliculi, which may be due to damage of the nigral GABAergic projection to this brain area. In animals with unilateral ibotenic acid lesions of the tuberomammillary nucleus, several markers of dopaminergic and serotonergic acitivity were increased in the neostriatum, tectum, and hippocampus. This effect may have been due to the loss of inhibition otherwise provided by the wide-ranging histaminergic output of the tuberomammillary nucleus. These results are discussed with respect to the major outputs of the three brain areas, their potential impacts on neurotransmitters in their projection sites, and their role in behavioral asymmetry.
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  • 81
    ISSN: 1432-1106
    Keywords: Key words Neural transplantation ; Tyrosine hydroxylase ; Calcium-binding proteins ; Parkinson’s disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or directly as dissociated cell suspensions, and compared with regard to neuronal survival and ability to normalize rotational behavior in adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received injections of cell-free medium and served as controls. The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 ± 98, mean ± SEM) and grafts of fresh, dissociated cell suspension (806 ± 105, mean ± SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after explantation, with an additional 23.1% loss after grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells in the cell-suspension grafts. Immunostaining for the calcium-binding proteins calretinin, calbindin, and parvalbumin showed no differences in the neuronal expression of these proteins between the two graft types. In conclusion, we found comparable dopaminergic cell survival and functional effects of tissue-culture grafts and cell-suspension grafts, which currently is the type of graft most commonly used for experimental and clinical grafting. In this sense the result is promising for the development of an effective in vitro storage of fetal nigral tissue, which at the same time would allow neuroprotective and neurotrophic treatment prior to intracerebral transplantation.
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  • 82
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Superior colliculus ; Nucleus of the optic tract ; Electrophysiology ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In most mammals the superior colliculus (SC) and the pretectal nucleus of the optic tract (NOT) receive direct input from the ipsilateral visual cortex via projection neurons from infragranular layer V. We examined whether these projection neurons belong to different populations and, if so, whether it is possible to correlate the electrophysiological features with the suggested function of these neurons. Projection cells were retrogradely labeled in vivo by rhodamine-coupled latex beads or fast blue injections into the SC or the NOT 2–5 days prior to the electrophysiological experiment. Intracellular recordings of prelabeled neurons were made from standard slice preparations and cells were filled with biocytin in order to reveal their morphology. Both cell populations consist of layer V pyramids with long apical dendrites that form terminal tufts in layer I. In electrophysiological terms, 12 of the corticotectal cells could be classified as intrinsically bursting (IB), while two neurons showed a doublet firing characteristic and one neuron was classified as regular-spiking (RS). Intracortical microstimulation of cortical layer II/III revealed that SC-projecting neurons responded optimally to stimulation sites up to a distance of 1000 μm from the recorded cell. The morphological features of the SC-projecting cells reveal an apical dendritic tuft in layer I with a lateral extension of 300 μm, a mean spine density of 65 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 13 boutons per 100 μm on the intracortical axons. Sixteen NOT-projecting neurons exhibited an IB and five cells an RS characteristic. Intracortical microstimulation of cortical layer II/III showed that NOT-projecting neurons responded optimally to stimulation sites up to a distance of 1500 μm. Their morphological features consist of an apical dendritic tuft with a lateral extension of 500 μm, a mean spine density of 25 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 6 boutons per 100 μm on the intracortical axons. When the passive membrane parameters, responses to intracortical microstimulation in layer V, the extension of the basal dendritic field, and spine densities in layers I or V were compared between SC- and NOT-projecting cells, no differences were revealed. Differences were only consistently found in the supragranular layers, either for morphological parameters or for intracortical microstimulation. The results suggest that NOT-projecting and SC-projecting neurons, although biophysically similar, could integrate and transmit different spatial aspects of cortical visual information to their target structures.
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  • 83
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    Experimental brain research 120 (1998), S. 461-469 
    ISSN: 1432-1106
    Keywords: Key words Hypoglycemic coma ; Specific gravity ; Brain edema ; Tissue osmolality ; Blood-brain barrier permeability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the effects of pronounced hypoglycemia on brain osmolality and brain edema formation, fasted rats were rendered hypoglycemic by injection of insulin, and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by glucose administration. The change in water content in different brain regions was measured as a change in specific gravity after 30 min of hypoglycemic coma, or 30, 60, and 180 min after glucose administration. Plasma and brain tissue osmolality were measured in separate animals. The results show a significant decrease in specific gravity (increase in water content) in all structures measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the period of coma, as well as after 30 min and 60 min of recovery. At 180 min of recovery, brain water was normalized. The edema affected all structures to the same degree regardless of their vulnerability to hypoglycemic damage. Brain tissue osmolality showed a tendency to decrease with decreasing tissue glucose content. The decrease was significant (P〈0.01) at 30 min of isoelectric coma. In the recovery phase, normal brain osmolality was restored within 30 min. Measurements of blood-brain barrier (BBB) permeability after 30 min of hypoglycemic coma showed no extravasation of Evan’s blue, though a small but significant increase in the permeability for aminoisobutyric acid (AIB) in caudoputamen and in cerebellum was found. To analyze the importance of tissue acidosis for formation of edema, hypoglycemic animals were made acidotic by increasing the CO2 concentration in inspired air to produce an arterial plasma pH of 6.8–6.9. In these animals the edema was of a similar degree to the normocapnic animals, and the permeability for AIB was normal. We conclude that osmolytic mechanisms are not the primary cause of the selective neuronal vulnerability in hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic insult.
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  • 84
    ISSN: 1432-1106
    Keywords: Key words Oncogene expression ; Polyamines ; Neuropathology ; Apoptosis ; Olfactory cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Microencephalic rats obtained by gestational treatment with the DNA alkylating agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic neuropathology caused by systemic injections of the convulsant neurotoxin kainic acid. Taking advantage of this, we have studied in these rats, as well as in normal rats, the relationship between the induction of cellular signals supposedly related to cell death and the neuronal apoptosis consequent to kainic acid administration. While normal rats responded to the excitatory insult with a large and relatively long lasting increase of the activity of the enzyme ornithine decarboxylase and of the concentration of putrescine in some brain regions, these alterations were much smaller in microencephalic rats. Expression of c-fos in brain regions sensitive to kainic acid was quicker but lasted a noticeably shorter time in microencephalic rats as compared to normal animals. A profusion of apoptotic neurons, labeled by an in situ technique, were observed in the olfactory cortex, amygdala and hippocampus of normal rats injected with kainic acid, in particular 48 h and 72 h after drug administration. At corresponding time intervals and with similar topographic localization, neurons expressing p53 protein were observed. By contrast, microencephalic rats displayed only in a few cases and in a small number apoptotic neurons in restricted areas of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases small populations of p53-expressing neurons were also present in the same areas. The present observations clearly show that oncogenes such as c-fos and p53, as well as ornithine decarboxylase which behaves as an immediate-early gene in the brain under certain circumstances, undergo noticeably lower and/or shorter induction in microencephalic rats exposed to excitotoxic stimuli. In these rats, therefore, the cellular signalling pathways studied here and related to excitotoxic sensitivity and committment to cell death are downregulated as a probable consequence of altered brain wiring.
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  • 85
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    Experimental brain research 121 (1998), S. 174-180 
    ISSN: 1432-1106
    Keywords: Key words Substance P ; Nerve growth factor ; Growth-associated protein 43 ; Nerve endings ; Myositis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The density of substance P (SP)-, calcitonin gene-related peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-immunoreactive (ir) nerve endings was quantitatively evaluated in intact and inflamed gastrocnemius-soleus muscle of the rat. In persistently inflamed muscle (12 days after a single injection of Freund’s adjuvant into the muscle), the density of SP-ir fibres was significantly increased. CGRP- and VIP-ir fibres displayed an insignificant increase in density. The density of fibres ir for nerve growth factor (NGF) and for growth-associated protein 43 (GAP-43/B-50), a marker for axonal sprouting, regeneration and synaptic reorganisation, increased significantly in persistently inflamed muscle. The data are consistent with the established contribution of NGF on the expression of SP and GAP-43 in afferent neurones under the influence of a persistent inflammation.
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  • 86
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    Experimental brain research 118 (1998), S. 551-563 
    ISSN: 1432-1106
    Keywords: Key words: Transplantation ; Calbindin D28K ; Parvalbumin ; Septum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study characterizes expression of calbindin D28 K (CB-D28 K) and parvalbumin (PV) in ventral forebrain (VFB) grafts placed in the neocortex of adult rats bearing quisqualic acid lesions to the nucleus basalis magnocellularis. Three to nine months after transplantation surgery, rats were killed for in situ hybridization with probes to CB-D28K or PV and for immunohistochemistry with antibodies to CB-D28K or PV. In addition, an antibody to choline acetyltransferase (ChAT) was used to characterize the cholinergic component in the graft and an antibody to tyrosine hydroxylase (TH) to explore catecholaminergic innervation of the graft. Quantitative analysis of CB-D28K and PV messenger ribonucleic acid (mRNA) was based on counts of silver grains generated by emulsion autoradiography. Cells expressing CB-D28K mRNA were significantly larger than such cells in the adult VFB and the mean number of silver grains per cell was significantly greater than to such cells in the adult VFB. The level of CB-D28K mRNA expression as calculated by ratio of silver grains per unit area was also significantly increased. Quantification of PV mRNA showed no significant differences between the cells in the graft and in the adult VFB. In order to begin to interpret these findings, a comparison was made with such cells in the VFB of developing rats. Brain sections were sampled from embryonic day 17 and postnatal days 1, 5, 12, 19 and adult (6–12 months of age). Cells expressing CB-D28K mRNA were detected in ventral forebrain from postnatal day 5 and cells expressing PV mRNA were detected in ventral forebrain from postnatal day 19. In the course of normal development of the ventral forebrain, no CB-D28K cells were found that were as large or expressed such high levels of CB-D28K mRNA as observed in the grafts. We conclude that changes in grafted cells expressing CB-D28K do not reflect an arrest of developmental processes. TH immunohistochemistry revealed lack of catecholaminergic innervation of the graft, whereas adult mediolateral septal cells that express CB-D28K receive such innervation in addition to other neurotransmitter inputs. Imbalance in neurotransmitter inputs to grafted cells expressing CB-D28K is discussed as a possible factor in their increased size and gene expression.
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  • 87
    ISSN: 1432-1106
    Keywords: Key words Thyroid hormone ; Neurotrophins ; Septum ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.
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  • 88
    ISSN: 1432-1106
    Keywords: Key words Glutamate receptor ; GABA ; Double immunostaining ; Colocalization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A recent study demonstrated both an extrinsic and an intrinsic calretinin (CR) innervation of the rat septal complex and that a population of the extrinsic calretinin fibers is aspartate/glutamate-containing. The aim of this study was to determine which types (GluR1, GluR2/3, or both) of AMPA receptor-containing lateral septal area neurons are innervated by extrinsic and intrinsic CR neurons and whether the intrinsic CR cells are GABAergic. Light- and electron-microscopic single immunostaining for CR, GluR1, and GluR2/3, as well as light- and electron-microscopic-double immunostaining experiments for CR plus GluR1 and CR plus GluR2/3 were performed in the lateral septal area. Furthermore, the ″mirror″ colocalization technique was employed on consecutive vibratome sections of the septal complex to investigate whether the intrinsic septal CR neurons are GABAergic. The results are summarized as follows: (1) both GluR1- and GluR2/3-immunoreactive neurons are innervated by CR-containing fibers; (2) the majority of these synapses, observed mainly on the soma and, to a lesser extent, on proximal dendrites of AMPA receptor-containing neurons, represent asymmetric synaptic membrane specializations; (3) a minority of CR-containing axon terminals associated with both GluR1- and GluR2/3-immunoreactive neurons form symmetric contacts, predominantly on their soma; and (4) 93% of the lateral septal area CR cells are GABAergic. These observations indicate that both GluR1- and GluR2/3-containing lateral septal area neurons receive a dual intrinsic and extrinsic CR innervation. The former (intrinsic) CR boutons are GABAergic, while the latter form asymmetric synaptic contacts, are excitatory, and probably originate in the supramammillary area, since previous work has demonstrated that a population of supramammillo-septal fibers contain aspartate and/or glutamate.
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  • 89
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    Experimental brain research 119 (1998), S. 159-165 
    ISSN: 1432-1106
    Keywords: Key words Neuropeptide FF ; Spinothalamic neurons ; Lateral cervical nucleus ; Lateral spinal nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Neuropeptide FF (NPFF, F8Famide) is best known for its modulating effect on opioid analgesia and morphine tolerance. However, the exact mode of action of NPFF in sensory transmission is not known. We compared the distribution of NPFF-immunoreactive (ir) fibers and terminal-like thickenings with the retrograde, tracer-filled spinothalamic (ST) neurons in the lateral spinal nucleus (LSN) and lateral cervical nucleus (LCN) of rat, areas where NPFF-containing nerve terminals are abundant. We injected fluorescent latex microspheres into the ventroposterolateral thalamic nucleus and more medial thalamic nuclei, which are innervated by ST neurons. We found NPFF-ir terminal-like thickenings and fibers apposing the tracer-filled neurons in the LSN and LCN. ST neurons filled with the retrograde tracer making contacts with NPFF-ir terminal-like thickenings, were found to terminate not only in the ventroposterolateral thalamic nucleus but also in more medial thalamic nuclei. The highest number of tracer-filled ST neurons having NPFF-ir terminal-like thickenings and fibers in apposition were found at the cervical level. Our results suggest that NPFF-containing systems in the spinal cord of rat are not limited to the substantia gelatinosa, and the sensory functions of NPFF may be mediated at least partly through the modulation of the ST system. NPFF-ir contacts in the LSN and LCN might play an important role in the somatic sensory transmission system. This study shows evidence for the first time that the spinal NPFF-containing system may be involved in mechanisms that control sensory input to the supraspinal levels.
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  • 90
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    Experimental brain research 122 (1998), S. 333-338 
    ISSN: 1432-1106
    Keywords: Key words Hypothermia ; Cerebral ischemia ; Glucose metabolism ; Middle cerebral artery occlusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37±0.5°C) and hypothermic (30±0.5°C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.
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  • 91
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    Experimental brain research 120 (1998), S. 335-344 
    ISSN: 1432-1106
    Keywords: Key words Plasticity ; Glutamate ; AP5 ; Visual Deprivation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  N-methyl-D-aspartate (NMDA) receptor-mediated activity is considered important for experience-dependent plasticity in the developing visual system. We investigated the influence of age and experience on the role of NMDA receptors in the visual transmission in the superficial grey layer of the superior colliculus (SGS) of the superior colliculus, where, in the adult, NMDA receptors mediate a substantial part of the visual response. In normally reared (postnatal day 14, P14, to adult) rats, visual responses were challenged with NMDA receptor-selective iontophoretic applications of the antagonist D-2-amino-5-phosphonovalerate (AP5). After eye opening (at P14), there was a significant increase in the number of neurones whose visual responses were reduced during AP5 ejection, which peaked at P22 (85%; n = 21), and then declined to adult levels (66%; n = 47) at P25. The mean reduction of the response (from control levels) by AP5 was similar at all ages (approximately 40%). Dark rearing had striking effects on the role of NMDA receptors in visual transmission, especially when comparisons were made between age-matched subjects greater than P25. In these subjects, AP5 ejection reduced the visual responses of all neurones studied. In addition, AP5 ejection caused a significantly larger reduction of visual responses in dark-reared rats (mean reduction 62 ± 4; n = 29) compared with age-matched controls (mean reduction 44 ± 8; n = 23). The D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the visual responses of every neurone studied and there were no age- or experience-dependent effects. We conclude that NMDA receptors, but not AMPA receptors, assume greater importance for visual transmission in the SGS of dark-reared rats.
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  • 92
    ISSN: 1432-1106
    Keywords: Key words Stria terminalis ; Epinephrine ; Memory consolidation ; Two-way active avoidance ; Basic learning capacities ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rats received bilateral stria terminalis (ST) lesions or were sham-operated. Five days later, the animals were trained in a two-way active avoidance task (one session, 30 trials) and, immediately after the training session, received 0.01 mg/kg i.p. epinephrine or distilled water. Retention was tested 20 days after the acquisition session. In sham-operated groups, epinephrine improved retention in rats that were poor learners and impaired it in rats that were good learners. In poor learners with posttraining epinephrine, lesions of the ST not only blocked the facilitatory effect of epinephrine but also disrupted performance throughout the retention session. In good learners, ST lesions attenuated the disruptive effect of epinephrine. Lesions per se did not affect either acquisition or retention. We conclude that ST is involved in the modulatory effect of posttraining epinephrine on memory consolidation. In addition and considering the results observed in rats that were poor learners, we suggest that emotional factors and/or other amygdaloid pathways different from the ST could participate in the effects of posttraining epinephrine, along with the ST.
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  • 93
    ISSN: 1432-1106
    Keywords: Key words Metabotropic glutamate receptors ; 2R ; 4R-4-Aminopyrrolidine-2 ; 4-dicarboxylate ; Somatosensory thalamus ; Presynaptic inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recordings were made from single neurones responsive to somatosensory input in the ventrobasal thalamus of the anaesthetised rat. GABAergic afferent inhibition arising from the thalamic reticular nucleus was evoked using a condition-test vibrissal stimulation paradigm. Local iontophoretic application of the group II metabotropic glutamate receptor (mGluR) agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the vicinity of the recorded neurones produced a reduction of the afferent inhibition (from 78±3.0% to 25±5.3%), presumably via a presynaptic mechanism. This effect could be antagonised by LY307452, a known group II mGluR antagonist. In contrast, two selective group I mGluR agonists, (S)-3,5-dihydroxyphenylglycine (DHPG) and trans-azetidine-2,4-dicarboxylate (tADA), were without effect on the GABAergic inhibition. These data show that group II but not group I mGluRs can have a significant role in the modulation of GABAergic afferent inhibition in the ventrobasal thalamus. This could be of importance in the control of sensory discriminative processes and functions of sleep, arousal and seizure generation.
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  • 94
    ISSN: 1432-1106
    Keywords: Key words GABAA-receptor α1-subunit ; Parvalbumin ; Striatum ; Pallidum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ventral striatum is more closely related to limbic brain regions than the dorsal striatum in spite of the remarkable similarities in the structural organization between these two brain regions. The present study is focused on the comparison of ventral striatopallidal territories and the dorsal striatopallidal system regarding the GABAA-receptor α1-subunit and parvalbumin immunoreactivity, as these markers showed specific distribution patterns and coexpression sites in the more intensely studied dorsal regions. Our investigations revealed that: (1) Parvalbumin single-labeled cells and a moderate number of neurons single-labeled with the GABAA-receptor α1-subunit exist not only in the dorsal but also in the ventral striatum, including the striatal cell bridges. In addition, morphologically similar neurons positive for the α1-subunit were also found in the corpus callosum and anterior commissure. (2) A small number of double-labeled neurons was seen not only in dorsal but also in ventral striatal regions. Such cells were mainly located near the border with the globus pallidus and ventral pallidum. They are likely to represent a further type of striatal neuron. (3) The vast majority of neurons in the entopeduncular nucleus, the homologue of the primate internal globus pallidus segment, coexpressed α1-subunit and parvalbumin immunoreactivity, as reported previously for the other pallidal compartments. (4) The islands of Calleja adjoining the ventral pallidal extensions in the olfactory tubercle exhibited a strong α1-subunit immunoreactivity in the neuropil as well as somata single- or double-labeled for both markers. Our findings indicate that the dorsal and ventral striatopallidal compartments are similarly organized in general with respect to the occurrence and distribution of single- and double-labeled parvalbumin-immunoreactive and GABAA-receptor α1-subunit-immunoreactive neurons.
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  • 95
    ISSN: 1432-1106
    Keywords: Key words Primary somatosensory cortex ; Forepaw skin map ; Environmental enrichment ; Cortical plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The cortical forepaw area of young adult rats was mapped by recording the response properties of small clusters of neurons in layer IV of the primary somatosensory (SI) cortex. First we quantitatively analyzed the somatotopic organizational features of the cortical forepaw representation in terms of areal extent and topography, receptive field (RF) sensory modality, size, and location. We also assessed the influence of environmental enrichment, known to induce structural alterations in cortical connectivity, on the representational characteristics of the forepaw maps. Long-Evans rats were housed in environments (standard, SE; enriched, EE) promoting differential tactile experience for 71–113 days from weaning. Within the SI, we found a single and complete topographic map of the cutaneous surfaces of the forepaw consisting of a rostrolateral-caudomedial sequence of digit and pad representational zones. Small islets of noncutaneous responses (NCR; high-threshold, deep-receptor input) within the boundaries of the cutaneous maps were a conspicuous feature of the forepaw map for SE rats. These islets created discontinuities in the representation of contiguous skin territories. In the SE rats, about 79% of the cortical sites activated by light tactile stimulation had a single cutaneous RF, whereas about 21% exhibited multiple RFs. Most single-digit RFs we delineated in the SE rats extended across two or three phalanges. As a result, the representations of the phalangeal skin surfaces were not segregated but formed an overlapping continuum. Moreover, within these regions, as the electrode was displaced in regular steps across the mediolateral axis, RFs did not shift across the digit skin surface in an orderly manner, suggesting a lack of internal topography in the finger representation zones. Tactile experience promoted by environmental enrichment induced alterations in the representational features of the SI cutaneous map of the forepaw. In EE rats, the areal extent of the forepaw cutaneous representation was 1.5 times larger than in SE rats. Indeed, the cutaneous map extended into NCR cortical sectors along its external margins and also into NCR islets found in the forepaw area. Consequently, in EE rats there were fewer representational discontinuities. The areal enlargement was due to a selective increase in the areal extent of the glabrous but not the hairy skin surface representations. Furthermore, protuberant glabrous skin (digit tips, palmar pads) was represented over larger cortical regions than were other glabrous skin territories less likely to be stimulated during object palpation and manipulation. Maps from EE rats were also characterized by a larger proportion of sites with single RFs (88% compared with 79%). In addition, glabrous RFs from EE rats were smaller and more clustered on the digit tips and palmar pads than were RFs in SE rat maps. RF size on hairy skin surfaces remained unchanged. Because the RFs were smaller, the cutaneous maps of EE rats contained distinct representations of digit phalangeal glabrous skin. RFs tended to exhibit more orderliness in their progression across the digit glabrous skin of EE rats than they did in SE rats. The phalanges of EE rats were represented in distinct patches. Neurons in EE rats were more sensitive to light tactile stimulation than were neurons in SE rats. These alterations were presumably mediated by the selective potentiation of cutaneous over deep-receptor activation. More generally, the present study corroborates the view that cortical cutaneous maps are maintained in a permanent state of use-dependent fluctuation.
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  • 96
    Electronic Resource
    Electronic Resource
    Springer
    International journal of biometeorology 41 (1998), S. 101-104 
    ISSN: 1432-1254
    Keywords: Key words Space flight ; Rat ; Plantaris muscle ; GLUT-4 ; Citrate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract  The effects of 14 days of space flight on the glucose transporter protein (GLUT-4) were studied in the plantaris muscle of growing 9-week-old, male Sprague Dawley rats. The rats were randomly separated into five groups: pre-flight vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch; flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after the return from space; and synchronous ground controls (SC-R0 and SC-R9) sacrificed at the same time as the respective flight groups. The flight groups F-R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module located in the cargo bay of the shuttle transport system – 58 of the manned Space Shuttle for the NASA mission named ”Spacelab Life Sciences 2”. Body weight and plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC. Neither body weight nor plantaris muscle weight in either group had changed 9 days after the return from space. As a result, body weight and plantaris muscle weight did not differ between the flight and synchronous control groups at any of the time points investigated. The GLUT-4 content (cpm/µg membrane protein) in the plantaris muscle did not show any significant change in response to 14 days of space flight or 9 days after return. Similarly, citrate synthase activity did not change during the course of the space flight or the recovery period. These results suggest that 14 days of space flight does not affect muscle mass or GLUT-4 content of the fast-twitch plantaris muscle in the rat.
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  • 97
    Electronic Resource
    Electronic Resource
    Springer
    Intensive care medicine 24 (1998), S. 61-70 
    ISSN: 1432-1238
    Keywords: Key words Blood vessels ; Kidney ; Renal circulation ; Renal vascular resistance ; Calcium ; Ionized calcium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Calcium may be indicated in critically ill patients for hemodynamic support. Its well-known action includes peripheral vasoconstriction. Vascular effects of calcium are unknown, however, in the presence of hypertension or in combination with calcium channel blocking drugs, commonly prescribed in the treatment of hypertension. The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitable study model, because their vascular reactivity closely agrees with that in hypertensive humans. The present study should clarify (a) are the renal vessels of SHR responsive to high and low ionized calcium ([Ca++] within the clinical ranges? (b) because release of nitric oxide is calcium ion dependent, are renal vascular responses altered after inhibition of NO synthase? (c) are vascular responses of SHR to hypercalcemia altered by the calcium channel blocking drug verapamil? Animals and interventions: We compared isolated kidneys of SHR and those of two strains of age-matched normotensive rats (NTR) in their responses to high and low [Ca++]. They were perfused with oxygenated, warmed (37 °C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady state high [Ca++] (1.88 mmol/l) and low [Ca++] (0.55 mmol/l) were instituted in randomized order. In protocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with NG monomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca++] levels were instituted in SHR after verapamil pretreatment. At each [Ca++] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mm Hg. Results: In SHR (perfusion pressure 100 mm Hg), high [Ca++] induced a decrease in renal flow (–11.8 ± 1.8 % of control), which was significantly greater (p 〈 0.05) than the change (− 6.1 ± 1.5 and − 6.9 ± 1.4 % of control) recorded in the two normotensive strains. In SHR (perfusion pressure 150 mmHg), high [Ca++] induced a decrease in renal flow (− 12 ± 1.3 % of control), also significantly greater (p 〈 0.05) than the changes (− 6.2 ± 1.1 and −5.8 ± 1.7 % of control) in the two normotensive strains. Similar differences and significances were again observed after L-NMMA pretreatment. In SHR, verapamil prevented renal vascular responses in SHR to both high and low [Ca++]. Conclusions: First, renal vascular responses to high [Ca++] in SHR are exaggerated. At the upper end of the hypercalcemia range the observed changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticipated to be even less pronounced. Second, effects of high [Ca++] were abolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hypertension.
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  • 98
    ISSN: 1432-198X
    Keywords: Key words: Hypercalciuria ; Idiopathic hypercalciuria ; 1 ; 25-Dihydroxyvitamin D ; Furosemide ; Ammonium chloride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Hypercalciuria was induced in female Sprague-Dawley rats, aged 40±2 days, by 7-day administration (mean±SEM) of calcitriol (5.4±0.1 ng/100 g per day, intraperitoneal), furosemide (14.9±1.9 mg/100 g per day, oral), or ammonium chloride (3.8±0.1 mEq/100 g per day, oral). Calciuria increased from 1.9±0.2, 1.6±0.2, and 1.9±0.3 to 5.4±0.5, 4.0±0.9, and 5.4±0.5 mg/100 g per day in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC, n = 10) groups, respectively. Calciuria did not change (1.9±0.3 vs. 1.6±0.1 mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats became hypercalciuric as assessed by urine calcium excretion above the 90th percentile of normal values. Hypercalciuria was of similar degree in the three groups of rats and was not associated with hypercalcemia, metabolic acidosis, severe serum electrolyte imbalance, or growth impairment. VD rats had low serum parathyroid hormone (PTH) concentrations (3.0±0.5 pg/ml vs. 15.8±1.3 pg/ml in controls, P 〈0.05), whereas serum PTH was not significantly elevated in F rats (16.2±1.8 pg/ml). Thus, the protocol caused three forms of hypercalciuria that mimicked the clinical conditions of idiopathic hypercalciuria in humans and may clearly be differentiated according to their mechanism of production. This experimental model of normocalcemic hypercalciuria may be useful to clarify unknown aspects of pathogenesis and pathophysiology of idiopathic hypercalciuria in children.
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  • 99
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; Fear-potentiated startle response ; 8-OH-DPAT ; Flesinoxan ; WAY 100 ; 635 ; (±)-Pindolol ; DU 125 ; 530 ; Lower lip retraction ; 5-HT1A receptor agonist ; 5-HT1A receptor antagonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study investigated whether the anxiolytic effect of 5-HT1A receptor agonists on the fear-potentiated startle response could be antagonized by 5-HT1A receptor antagonists. Therefore, control and fear-potentiated startle amplitudes were measured after co-administration of vehicle, flesinoxan (10 mg/kg PO) or 8-OH-DPAT (0.3 mg/kg SC) and DU 125,530 (0, 1, 3 and 10 mg/kg SC), (±)-pindolol (0, 3, 10 and 30 mg/kg SC) or WAY 100,635 (0, 0.1, 0.3 and 1 mg/kg SC). Unexpectedly, the three antagonists themselves as measured in the vehicle-pretreatment groups dose-dependently decreased startle potentiation. Further, DU 125,530 and WAY 100,635 were able to reverse the attenuating effect of 8-OH-DPAT, while no antagonism of the flesinoxan effect on startle potentiation was found. In contrast, both the flesinoxan- and 8-OH-DPAT-induced lower lip retraction were antagonized by DU 125,530 and WAY 100,635, but not by (±)-pindolol. The findings of the present study suggest that drugs acting on 5-HT1A receptors differentially affect lower lip retraction and startle potentiation probably mediated by different neuronal populations.
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  • 100
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 135 (1998), S. 392-400 
    ISSN: 1432-2072
    Keywords: Key words Neuroleptic ; Clozapine ; Haloperidol ; Loxapine ; Amphetamine ; Pentylenetetrazole ; Sertindole ; Seroquel ; Olanzapine ; Risperidone ; JL13 ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The discriminative stimulus properties of the prototypical atypical neuroleptic clozapine (5 mg/kg, IP) were characterised in rats using a fixed ratio assay. Clozapine induced full dose-related generalization in the absence of response suppression. Amphetamine and pentylenetetrazol failed to generalise at doses known to be discriminable, showing a degree of specificity for the clozapine cue. The typical neuroleptics haloperidol and loxapine induced minimal (20%) generalization at doses with marked behavioural effects; thus clozapine discrimination dissociates clozapine from typical neuroleptics. Atypical neuroleptics which are not clozapine congeners produced weak partial generalization when tested up to the highest doses that could be studied. The maximal levels of generalization induced by these agents were: amisulpiride 28%, risperidone 40% and sertindole 50%. Clozapine congeners typically caused more generalization, the novel pyridobenzoxapine JL13 inducing 70% maximal generalization. Most generalization (83%) was seen with the clozapine congener seroquel, although in contrast to clozapine, it only generalised at doses with marked effects on responding, so that no drug mimicked clozapine fully. Surprisingly, the clozapine congener olanzapine only induced a maximal level of 38% generalization. This apparently anomalous finding is attributed to an inability to test high doses of the drug due to its rate-suppressant actions. The clozapine cue can be used to rank atypical neuroleptics in terms of their similarity to clozapine in vivo. The clozapine cue is probably a compound cue, since only agents showing “polyvalent” receptor pharmacology induced substantial generalization.
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