Signalling by the fungus Pythium ultimum represses expression of two ribosomal RNA operons with key roles in the rhizosphere ecology of Pseudomonas fluorescens F113.

Pseudomonas fluorescens F113 produces antifungal metabolites that protect the roots of sugarbeet from the fungus Pythium ultimum. The phytopathogen, in turn, has the ability to downregulate the expression of genes fundamental to the rhizosphere competence of the bacterial strain. This paper describes the characterization of two of these genes, which were isolated by screening a mini-Tn5::lacZ mutant bank for differential expression of beta-galactosidase in the presence of P.

Exchange nailing for femoral shaft aseptic non-union.

Although rare, non-union of femoral shaft fractures is a cause of significant morbidity. In aseptic non-union, excellent union rates have historically been reported following reamed exchange femoral nailing. However, recently, a high incidence of failure requiring additional procedures has been reported.

GABA receptors and benzodiazepine binding sites modulate hippocampal acetylcholine release in vivo.

In the present study, the regulation of acetylcholine release from the ventral hippocampus by gamma-aminobutyric acid (GABA) was investigated in vivo. GABA receptor agonists and antagonists were administered locally in the medial septum and the adjacent vertical limb of the diagonal band of Broca, or in the hippocampus by retrograde dialysis. Acetylcholine release was measured in the ventral hippocampus.

Atypical antipsychotic-like effects of the dopamine D3 receptor agonist, (+)-PD 128,907.

Anti-schizophrenia agents with improved efficacy and side-effect profiles are required. A dopamine D3 receptor agonist, R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3- b]-1,4-oxazin-9-ol HCl ((+)-PD 128,907), displayed an atypical antipsychotic profile comparable to that of clozapine. (+)-PD 128,907 blocked stereotypy produced by dizocilpine (MK-801) at 12-fold lower doses than those affecting apomorphine-induced stereotypes in mice and did not produce catalepsy.

Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic.

The trifluoromethanesulfonyloxy (TfO) analogues 3 and 4 of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine (clozapine, 1) and its 2-chloro isomer (iso-clozapine, 2), respectively, were synthesized via their OMe and OH analogues with the conventional synthetic method of the tricyclic dibenzodiazepines and evaluated pharmacologically along with their parent drugs. The binding profile of the 2-OTf analogue (4) is comparable to the binding profile of 1, although the affinity for the dopamine (DA) D2 receptors is higher (IC50 values are 31 nM and 330 nM for compounds 4 and 1, respectively). Interestingly, no notable affinity for muscarinic receptors could be detected in compound 4.

Substantia nigra D1 receptors and stimulation of striatal cholinergic interneurons by dopamine: a proposed circuit mechanism.

Dopamine release can regulate striatal acetylcholine efflux in vivo through at least two receptor mechanisms: (1) direct inhibition by dopamine D2 receptors on the cholinergic neurons, and (2) excitation initiated by dopamine D1 receptors. The neuroanatomical locus of the latter population of D1 receptors and the pathway(s) involved in the expression of their influence are controversial issues. We have tested the hypothesis that D1 receptors in substantia nigra pars reticulata are involved in the excitatory component of dopaminergic actions on striatal acetylcholine output.

Effect of monoamine oxidase A and B and of catechol-O-methyltransferase inhibition on L-DOPA-induced circling behavior.

The effect of enzyme-inhibiting adjuvants on L-DOPA + benserazide-induced contralateral turning in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats was studied. Both the number of turns and the duration of turning were examined. Inhibition of MAO-A with 10 mg/kg Ro 41-1049 increased both parameters; inhibition of COMT with 30 mg/kg Ro 40-7592 had a similar effect.

Spontaneous release of acetylcholine in striatum is preferentially regulated by inhibitory dopamine D2 receptors.

The dose-related effects of the direct dopamine D2 receptor agonist quinpirole [trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1 H-pyrazolo[3,4-g]quinoline] on the extracellular concentrations of dopamine and acetylcholine in rat striatum were measured using in vivo microdialysis. Quinpirole was administered intraperitoneally at doses of 3, 30, 300, and 3000 micrograms/kg. Acetylcholine measurements were conducted in the presence of 10 nmol/l of the acetylcholinesterase inhibitor neostigmine in the microdialysis perfusate.

Septal and hippocampal glutamate receptors modulate the output of acetylcholine in hippocampus: a microdialysis study.

In the present study, glutamate receptor agonists and antagonists were administered by retrograde microdialysis into either the medial septum/vertical limb of the diagonal band (MS/vDB), or hippocampus, and the output of acetylcholine (ACh) was measured in the hippocampus by using intracerebral microdialysis. Perfusion with N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) in the MS/vDB caused an incrase in ACh output in the hippocampus. This increase was completely blocked by coadministration of their respective antagonists D(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX).

Physiological release of striatal acetylcholine in vivo: modulation by D1 and D2 dopamine receptor subtypes.

Our experiments assessed the modulation of striatal acetylcholine (ACh) output by dopamine (DA) receptor subtypes under physiological conditions using in vivo microdialysis in awake rats. The degree to which the dopaminergic modulation of striatal cholinergic neurons might vary as a function of local extracellular ACh level also was examined by application of varying concentrations of the acetylcholinesterase (AChE), inhibitor neostigmine (NEO) in the microdialysis perfusate. Under physiological conditions (O NEO), the amount of ACh in the dialysates was 25.

Characterisation of muscarinic autoreceptors in the septo-hippocampal system of the rat: a microdialysis study.

The effects of local administration of cholinergic drugs on the release of acetylcholine in the septo-hippocampal system were investigated using intracerebral microdialysis. Dialysis probes were implanted in the cell-body area of septo-hippocampal neurones in the medial septal area, and in the terminal area of the same neurones in the ventral hippocampus. Drugs were administered locally via the dialysis probe.

Changes in mRNAs for enzymes of glutamine metabolism in kidney and liver during ammonium chloride acidosis.

Changes in protein and mRNAs for enzymes of glutamine metabolism were determined in rat kidney cortex at different times after induction of NH4Cl acidosis. After NH4Cl, phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 16-fold by 10 h (P < 0.05) and then returned to control levels by 30 h.

GABAergic modulation of striatal cholinergic interneurons: an in vivo microdialysis study.

Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABAA and the GABAB receptor. Using in vivo microdialysis, we have studied the effect of intrastriatal application of the GABAA-selective compounds muscimol and bicuculline and the GABAB-selective compounds baclofen and 2-hydroxysaclofen, agonists and antagonists, respectively, at GABA receptors, on the output of striatal acetylcholine (ACh).

Differential effect of systemic administration of bromocriptine and L-dopa on the release of acetylcholine from striatum of intact and 6-OHDA-treated rats.

A presumed balance between striatal dopaminergic and cholinergic systems forms a major theoretical framework for the development of new agents for the treatment of Parkinson's disease. We therefore studied the effect of two drugs currently used as anti-parkinsonian agents, bromocriptine (BROMO) and L-beta-3,4-dihydroxyphenylalanine (L-DOPA), on the release of striatal acetylcholine (ACh) in intact and 6-hydroxy-dopamine-treated rats using in vivo microdialysis. Lesioned rats with a > 90% tissue depletion of striatal dopamine (DA) had a significantly higher output of striatal ACh than unlesioned rats (88 fmol/min vs.

A pilot study for a structured, time-limited therapy group for sexually abused pre-adolescent children.

The critical role of specific types of mastery skill development in the treatment of sexually abused children is explored, and defense mechanisms of "invulnerable children," who function adequately despite trauma and stress, are described. The authors describe their development of structured group therapy techniques designed to foster these types of mastery skills with sexually abused children aged 6 to 8. These techniques include development of intellectualization defenses through original coloring books and therapeutic board games, cathartic exploration of feelings through structured art and storytelling exercises, cognitive relabeling and self-esteem building through role-play, "chants and cheers," homework shared with mothers, and other structured group procedures designed to develop specific coping skills.