Search PubMed⌕ Search

Biomedical subjects

G Hans

Publications and source records attributed to G Hans.

13 recordsLinked to original sources
PubMed2004

[Transient ischemic attacks: a new definition].

According to its initial definition, which dates back more than 50 years, a transient ischemic attack (TIA) is a sudden focal neurologic deficit lasting for less than 24 hours, of presumed vascular origin, and confined to an area of the brain or eye perfused by a specific artery. Recent data on the pathophysiology of cerebral ischemia and the progress made by the imaging techniques have led an American TIA Working Group to propose a new definition which states that: "A transient ischemic attack is a brief episode of neurologic dysfunction, caused by local brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of cerebral infarction". The advantages and limitations of this new definition, the need for an emergency medical care in the presence of a TIA, the clinical signs associated with this condition, the diagnostic work up, and the differential diagnosis are briefly discussed. A clinical example illustrates the difficulties that can be encountered in a case of TIA.

Brain Ischemia↗
PubMed2003

Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways.

In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The presence of SP high affinity neurokinin-1 receptor (NK1) transcripts was detected in the spiral ganglion and the NK1 protein localized to SGNs both ex vivo and in vitro. Treatment with SP increased cytoplasmic Ca2+ in SGNs, further arguing for the presence of functional NK1 on these neurons. Both SP and the agonist [Sar9,Met(O2)11]-SP significantly decreased SGN cell death induced by TFD, with no effect on neurite outgrowth. The survival promoting effect of SP was blocked by the NK1 antagonist, WIN51708. Both pan-caspase inhibitor BOC-D-FMK and SP treatments markedly reduced activation of caspases and DNA fragmentation in trophic factor deprived-neurons. The neuroprotective action of SP was antagonised by specific inhibitors of second messengers, including 1.2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, the protein kinase C (PKC) inhibitors bisindolylmaleimide I, Gö6976 and LY333531 and the MAPK/ERK inhibitor U0126. In contrast, nifedipine, a specific inhibitor of l-type Ca2+ channel, and LY294002, a phosphatidylinositol-3-OH kinase (PI3K) inhibitor, had no effect on SP trophic support of SGNs. Moreover, activation of endogenous PKC by 4 beta-phorbol 12-myristate 13-acetate (PMA) also reduced the loss of trophic factor-deprived SGNs. Thus, NK1 expressed by SGNs transmit a survival-promoting regulatory signal during TFD-induced SGN cell death via pathways involving PKC activation, Ca2+ signalling and MAPK/ERK activation, which can be accounted for by an inhibition of caspase activation.

Animals↗
PubMed2003

[Controversies in the secondary prevention of stroke].

Stroke is the third leading cause of death and the main cause of prolonged disability of adults in industrialised countries. After a first transient ischemic attack or a first minor stroke, the risk of recurrence is 16 folds higher than in control subjects. Therefore each patient suspect of a first ischemic cerebral event should be evaluated for the presence of a specific cause which could be treated. If such a cause is not found, platelet antiaggregant medications should be started.

Atrial Fibrillation↗
PubMed2003

[Statins for the brain?].

Whether cholesterol lowering decreases risk of stroke has long remained unclear. Large epidemiological studies have found only weak links between cholesterol levels and stroke. Recent studies with statins, more potent cholesterol lowering agents, have now demonstrated significant reductions of stroke incidence and total mortality when administered for secondary prevention in patients with wide ranges of cholesterol values. It remains unknown if a statin is superior to others for the secondary prevention of stroke.

Brain↗
PubMed2002

The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents.

1. In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra) may involve modulation of inhibitory neurotransmission. 2. GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide. 3. LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4. These minor direct effects contrasted with a potent ability of LEV (EC(50)=1 - 10 microM) to reverse the inhibitory effects of the negative allosteric modulators zinc and beta-carbolines on both GABA(A) and glycine receptor-mediated responses. 5. Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of beta-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6. LEV (17 mg kg(-1)) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the beta-carboline FG 7142, from a dose of 5 mg kg(-1). In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg(-1)) was without any effect on the protection afforded by LEV. 7. The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV.

Allosteric Regulation↗
PubMed2001

Local injection of endothelin-1 produces pain-like behavior and excitation of nociceptors in rats.

Neurobehavioral and neurophysiological actions of the peptide endothelin-1 (ET-1) were investigated after subcutaneous plantar hindpaw injections in adult male Sprague Dawley rats. Hindpaw flinching developed within minutes after ET-1 (8-16 nmol) injection, peaked at 30 min, lasted for 60 min, and was strongly inhibited by the endothelin-A (ET(A)) receptor antagonist, BQ-123 (3.2 m). In separate experiments, impulse activity of single, physiologically characterized sensory C-, Adelta-, and Abeta-fibers was recorded from the sciatic nerve in anesthetized rats after subcutaneous injections of endothelin-1 (1-20 nmol), alone or together with BQ-123 (3.2 m), into the plantar hindpaw receptive fields of these units. All nociceptive C-fibers (31 of 33 C-fibers studied) were excited by ET-1 (1-20 nmol) in a dose-dependent manner. For doses of 16-20 nmol, the mean latency for afferent activation after injection of ET-1 was 3.16 +/- 0.31 min, and the mean and maximum response frequency were 2.02 +/- 0.48 impulses (imp)/sec and 14.0 +/- 3.2 imp/sec, respectively. All 10 nociceptive Adelta-fibers (of 12 Adelta-fibers studied) also responded to 1-20 nmol of ET-1 in a dose-dependent manner with a mean latency of 3.5 +/- 0.12 min and mean response frequency of 3.3 +/- 2.3 imp/sec. In contrast, most Abeta-fibers (9 of 12) did not respond to ET-1. BQ-123, when coinjected with ET-1, blocked ET-1-induced activation in all C- and Adelta-fibers tested. These data demonstrate that subcutaneous administration of ET-1 to the rat plantar hindpaw produces pain-like behavior and selective excitation of nociceptive fibers through activation of ET(A) receptors.

Action Potentials↗
PubMed2001

Levobupivacaine combined with sufentanil and epinephrine for intrathecal labor analgesia: a comparison with racemic bupivacaine.

UNLABELLED: We performed a randomized, double-blinded study to compare levobupivacaine with racemic bupivacaine for labor analgesia. Eighty term parturients received either levobupivacaine 0.125% or racemic bupivacaine 0.125%, to which was added sufentanil 0.75 microg/mL and epinephrine 1.25 microg/mL. As part of a combined spinal-epidural procedure, 2 mL of this mixture was initially injected intrathecally, and the same solutions were subsequently administered epidurally. For both combinations, onset until the first painless contraction was 4 to 5 min. Most patients were pain free during the second contraction. The duration of initial spinal analgesia was 93.5 +/- 20 min and 94.7 +/- 31 min for levobupivacaine and racemic bupivacaine, respectively. The duration of analgesia for the first epidural top-up dose was also similar in the two groups. Total local anesthetic requirements during labor were not different. The only major difference observed was the absence of motor impairment in levobupivacaine-treated parturients as compared with the Racemic Bupivacaine group, in which the incidence of a Bromage-1 motor block was 34%. Other side effects and obstetric or neonatal outcomes were not different between groups. Intrathecal levobupivacaine has a similar clinical profile as racemic bupivacaine, but at equal doses it produced less motor block. IMPLICATIONS: When used intrathecally and epidurally for labor analgesia, levobupivacaine had the same clinical profile as racemic bupivacaine, but at equal doses it produced less motor block.

Adult↗
PubMed2000

Glycine triggers an intracellular calcium influx in oligodendrocyte progenitor cells which is mediated by the activation of both the ionotropic glycine receptor and Na+-dependent transporters.

Using fluo-3 calcium imaging, we demonstrate that glycine induces an increase in intracellular calcium concentration ([Ca2+]i) in cortical oligodendrocyte progenitor (OP) cells. This effect results from a calcium entry through voltage-gated calcium channels (VGCC), as it is observed only in OP cells expressing such channels, and it is abolished either by removal of calcium from the extracellular medium or by application of an L-type VGCC blocker. Glycine-triggered Ca2+ influx in OP cells actually results from an initial depolarization that is the consequence of the activation of both the ionotropic glycine receptor (GlyR) and Na+-dependent transporters, most probably the glycine transporters 1 (GLYT1) and/or 2 (GLYT2) which are colocalized in these cells. Through this GlyR- and transporter-mediated effect on OP intrcellular calcium concentration [Ca2+]i, glycine released by neurons may, as well as other neurotransmitters, serve as a signal between neurons and OP during development.

Amino Acid Transport Systems, Neutral↗
PubMed1998

Behavioral signs of acute pain produced by application of endothelin-1 to rat sciatic nerve.

We examined whether endothelin-1 (ET-1), a potent vasoconstrictive peptide secreted in high concentration by metastatic prostate cancer cells, produces endothelin receptor-dependent pain behavior when applied to rat sciatic nerve. ET-1 (200-800 microM) applied to the epineurial surface of rat sciatic nerve produced reliable, robust, unilateral hindpaw flinching lasting 60 min. Pre-emptive systemic morphine completely blocked this effect in a naloxone-reversible manner, suggesting that this behavior was pain-related. Equipotent doses of epineurially applied epinephrine had no effect, suggesting that ET-1 effects are on tissue sites other than sciatic nerve microvessels. Prior and co-administration of BQ-123, an endothelin-A (ET(A)) receptor antagonist, also blocked ET-1-induced hindpaw flinching establishing that pain behavior induced by ET-1 application to rat sciatic nerve is ET(A) receptor mediated.

Acute Disease↗
PubMed1998

Behavioral assessment of facial pain in rats: face grooming patterns after painful and non-painful sensory disturbances in the territory of the rat's infraorbital nerve.

Noxious stimulation of the rat's face evokes intense face grooming with face wash strokes almost exclusively directed to the stimulated area (e.g. Clavelou et al., Neurosci. Lett., 14 (1989) 3263-3270). Similar asymmetric face grooming behavior has been observed after transection (Berridge and Fentress, J. Neurosci., 6 (1986) 325-330) and chronic constriction of the infraorbital nerve (Vos et al., J. Neurosci., 14 (1994) 2708-2723). In the present study, the relation between unilateral facial pain and asymmetric face grooming was experimentally studied in normal, intact rats: face grooming patterns evoked by non-painful sensory disturbances in the territory of the infraorbital nerve (i.c. unilateral vibrissae clipping, anesthetic infraorbital nerve blockade, application of mineral oil on vibrissae) were compared to those evoked by noxious facial stimulation (s.c. formalin injection in mystacial pad) and those observed in unstimulated control rats, using video-analysis. Only formalin-injected rats displayed significantly more face grooming activity directed to the affected infraorbital nerve territory than unstimulated control rats. Non-painful sensory disturbances (especially mineral oil application) induced an initial bout of directed face grooming; this response was transient and short-lasting. These observations suggest that directed face grooming can be used as a sign of unilateral facial pain in freely moving rodents; unilateral non-painful facial sensory disturbances do not lead to intense and persistent directed face grooming.

Animals↗
PubMed1998

Recent advances in the pharmacology of nerve-injury pain.

Nerve injury pain remains a complex clinical challenge. Although the development of animal models of nerve injury pain has aided our understanding of potential pathophysiologic mechanisms for this condition, effective treatment still remains beyond our reach. Several classes of agents appear to block pain behavior in these animal models and humans, but they are often limited in their use by low efficacy, or undesirable side-effects. A prerequisite for the improvement of nerve injury pain includes the development of clinically-relevant animal models in which therapeutic targets can be identified.

Analgesics↗