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At least 595 records · Page 33Linked to original sources
PubMed2003

New sacral neuromodulation lead for percutaneous implantation using local anesthesia: description and first experience.

PURPOSE: In functional urology today chronic stimulation of the sacral nerves has become one of the most accepted methods of stimulation treatment. Many studies have described the advantage of test stimulation prior to implanting the definitive system to enable effective patient selection. We studied a method aimed at improving lead anchoring by developing a self-blocking electrode with a simple placement procedure, in the process creating a 2-stage approach to full percutaneous implantation that allows a long screening period during the first temporary stimulation stage. MATERIALS AND METHODS: A new tined lead was specifically designed to allow minimally invasive percutaneous lead placement requiring no incision and no additional fascial anchoring. From September 2001 to November 2002, 15 consecutive patients (3 males and 12 females) 27 to 70 years old (mean age 49) underwent this procedure and were prospectively evaluated. No PNE test was performed. RESULTS: Following the first stage screening phase 12 patients were implanted with the implantable pulse generator (IPG), while 3 who did not respond positively to test stimulation (neurogenic voiding dysfunction, urge incontinence and neurogenic urge incontinence in 1 each) did not undergo IPG implantation and had the tined lead removed under local anesthesia. We did not observe any lead displacement during the screening period (average 38.8 days) or during followup of IPG implanted cases (average 11 months, range 5 to 19). CONCLUSIONS: Our results show that the new tined anchoring system is a reliable way to allow truly minimally invasive placement of the chronic lead.

Adult↗
PubMed2004

Percutaneous tibial nerve neuromodulation is well tolerated in children and effective for treating refractory vesical dysfunction.

PURPOSE: We evaluated pain tolerability and the preliminary results of percutaneous tibial nerve stimulation (PTNS) in children with unresponsive lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 23 children 4 to 17 years old with LUTS refractory to conventional treatment underwent PTNS at 12, 30-minute weekly sessions. Ten patients had idiopathic overactive bladder, 7 were in nonneurogenic urinary retention and 6 had neuropathic bladder. Ten children were carefully evaluated for pain during needle insertion and electrical stimulation using certain scoring systems, namely the faces pain rating scale, Children's Hospital of Eastern Ontario pain scale, visual analogue scale and Questionario Italiano del Dolore. Evaluation was done at the first, sixth and last sessions. An anxiety-depression test was administered. All 23 children underwent clinical and urodynamic evaluation before and after treatment. RESULTS: All except 1 patient completed treatment. An anxious-depressive trait was found in 7 of 10 children/parents on anxiety-depression testing. Regarding pain, the faces pain rating scale never showed the severe pain face, the Children's Hospital of Eastern Ontario scale showed signs of pain at the beginning of each stimulation but not at the end, and the visual analog scale generally showed a low score with a further decrease during the first (p = 0.05), sixth (p = 0.03) and twelfth (p = 0.02) sessions. The Questionario Italiano del Dolore score was significantly related to the affective component of pain (p = 0.002) and it decreased between the first and last sessions. The 10 children with overactive bladder had symptom improvement in 80%, incontinence was cured in 5 of 9 and urodynamics showed normalization of cystometric bladder capacity in 62.5% with no more unstable contractions in those who became continent. Symptoms improved in 71% of the children in urinary retention. One of 3 and 4 of 7 patients had incontinence and post-void residual urine cured, respectively. Urodynamics showed an improved detrusor pressure at maximum flow (p = 0.009) and flow rate (p = 0.005). Symptoms and urodynamics did not significantly change in the neuropathic bladder group. CONCLUSIONS: PTNS is safe, minimally painful and feasible in children. It seems helpful for treating refractive nonneurogenic LUTS.

Adolescent↗
PubMedDate not supplied

Hypothesized deficiency of guanine-based purines may contribute to abnormalities of neurodevelopment, neuromodulation, and neurotransmission in Lesch-Nyhan syndrome.

The Lesch-Nyhan syndrome is a devastating sex-linked recessive disorder resulting from almost complete deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT). The enzyme deficiency results in an inability to synthesize the nucleotides guanosine monophosphate and inosine monophosphate from the purine bases guanine and hypoxanthine, respectively, via the "salvage" pathway and an accelerated biosynthesis of these purines via the de novo pathway. The syndrome is characterized by neurologic manifestations, including the very dramatic symptom of compulsive self-mutilation. The neurologic manifestations may result, at least in part, from a mixture of neurodevelopmental (eg, a failure to "arborize" dopaminergic synaptic terminals) and neurotransmitter (eg, disruption of GABA and glutamate receptor-mediated neurotransmission) consequences. HPRT deficiency results in elevated extracellular levels of hypoxanthine, which can bind to the benzodiazepine agonist recognition site on the GABA(A) receptor complex, and the possibility of diminished levels of guanine-based purines in discrete "pools" involved in synaptic transmission. In addition to their critical roles in metabolism, gene replication and expression, and signal transduction, guanine-based purines may be important regulators of the synaptic availability of L-glutamate. Guanine-based purines may also have important trophic functions in the CNS. The investigation of the Lesch-Nyhan syndrome may serve to clarify these and other important neurotransmitter, neuromodulatory, and neurotrophic roles that guanine-based purines play in the central nervous system, especially the developing brain. A widespread and general deficiency of guanine-based purines would lead to impaired transduction of a variety of signals that depend on GTP-protein-coupled second messenger systems. This is less likely in view of a prominent localized pathologic effect of HPRT deficiency on presynaptic dopaminergic projections to the striatum. A possible more circumscribed effect of a deficiency of guanine-based purines could be interference with modulation of glutamatergic neurotransmission. Guanosine has been shown to be an important modulator of glutamatergic neurotransmission, promoting glial reuptake of L-glutamate. A deficiency of guanosine could lead to dysregulated glutamatergic neurotransmission, including possible excitotoxic damage. Unfortunately, although the biochemical lesion has been known for quite some time (ie, HPRT deficiency), therapeutically beneficial interventions for these affected children and adults have not yet emerged based on this elucidation. Conceivably, guanosine or its analogues and excitatory amino acid receptor antagonists could participate in the pharmacotherapy of this devastating disorder.

Animals↗
PubMed1983

Immunohistochemical localization of vasoactive intestinal polypeptide (VIP) in Merkel cells of various mammals: evidence for a neuromodulator function of the Merkel cell.

Since met-enkephalin-like substance has been demonstrated only in Merkel cells of some rodents but not of cat, dog, pig, and humans, Merkel cells of these species were analyzed by immunohistochemistry using a variety of different antisera for the occurrence of neuropeptides different from met-enkephalin. In various locations of all species investigated Merkel cells were found to be immunoreactive exclusively to vasoactive intestinal polypeptide (VIP) but not to any of the other antisera used. Thus, in mammalian Merkel cells, neuropeptides occur that are different from met-enkephalin. It is suggested that the Merkel cell-axon complex represents a complex regulatory system involving a presumptive receptor or modulator function whereby the Merkel cell may influence the threshold of the sensory nerve ending via release of a neuropeptide (VIP- or met-enkephalin-like material).

Animals↗
PubMed2005

Changes in the neuromodulators of the diffuse endocrine system of the alimentary canal of farmed rainbow trout, Oncorhynchus mykiss (Walbaum), naturally infected with Eubothrium crassum (Cestoda).

A histopathological and immunohistochemical study on the intestines of 45 specimens of farmed rainbow trout, Oncorhynchus mykiss (Walbaum), from Loch Awe, Scotland, revealed a number of cellular deviations in individuals naturally infected with the pseudophyllidean cestode Eubothrium crassum (Bloch, 1779). Twenty-five individuals (55.5%) were infected with an average worm burden of 18.84 +/- 4.06 (mean +/- SE) cestodes per host (range, 2-80 worms; total 471 worms). The cestodes, measuring an average 8.23 +/- 1.10 cm (mean +/- SE; range, 5.3-13.0 cm) in length, were found attached by their scolices to the mucosal lining of the distal portion of the pyloric caeca. Within the caeca, the strobila evoked a mild catarrhal enteritis, namely an enhanced mucus production with epithelial cellular desquamation, a leucocytic infiltration of the lamina propria-submucosa and vacuolization of the intestinal epithelial cells. Eosinophilic granular cells of the stratum granulosum exhibited granular depletion, while within the catarrh, the presence of a high number of rodlet cells was noticed. Immunohistochemically, the occurrence of E. crassum caused a significant reduction in the number of bombesin-, gastrin-releasing peptide and glucagon-like immunoreactive endocrine cells, but an increase in the relative densities of endocrine cells containing cholecystokinin-8- and gastrin-like substances. There were, however, no significant differences in the number of endocrine cells that were immunoreactive to secretin, neuropeptide Y and peptide histidine-isoleucine antisera in the digestive tracts of either the infected or non-infected O. mykiss.

Animals↗
PubMedDate not supplied

Cholinergic neuromodulation by ATP, adenosine and its N6-substituted analogues in guinea-pig ileum.

The effects of ATP, adenosine and N6-substituted adenosines, adenosine receptor agonists, on the twitch contraction of guinea-pig ileum evoked by transmural stimulation were evaluated. Adenosine and ATP produced an immediate and concentration dependent inhibition of the twitch, IC50 being 1.1 X 10(-5) mol/l and 1.2 X 10(-5) mol/l, respectively. N6-l-phenylisopropyl adenosine (L-PIA), N6-cyclohexyl adenosine (CHA) and N6-allyl adenosine also induced inhibitions which were gradual and persistent, IC50 being 2.6 X 10(-8), 2.7 X 10(-8) and 5.4 X 10(-7) mol/l, respectively. Dipyridamole (10(-7) mol/l), an adenosine uptake inhibitor, markedly augmented the inhibition evoked by adenosine and ATP, but not that by three N6-substituted adenosines, while theophylline (10(-4) mol/l) almost completely antagonized the inhibitory effects of all purine compounds. IC50 value of adenosine in the presence of dipyridamole (5 X 10(-7) mol/l) was shifted to the left about 50 times from the control, whereas that of L-PIA was virtually unchanged. Tissue-medium ratios indicating uptake of [3H]adenosine, [3H]ATP and [3H]CHA into the segment were 3.23 (s.e.m. = 0.59), 3.59 (s.e.m. = 0.78) and 0.41 (s.e.m. = 0.04), respectively. These results suggest that not only adenosine and ATP but also these N6-substituted adenosines are potent agonists for the P1 receptor, implying a similarity between P1 and A1 receptor in a functional role and these purine compounds may thereby modulate cholinergic neurotransmission by altering adenylate cyclase activity.

Adenosine↗
PubMed1998

Electrophysical properties, synaptic transmission and neuromodulation in serotonergic caudal raphe neurons.

1. We studied electrophysiological properties, synaptic transmission and modulation by 5-hydroxytryptamine (5-HT) of caudal raphe neurons using whole-cell recording in a neonatal rat brain slice preparation; recorded neurons were identified as serotonergic by post-hoc immunohistochemical detection of tryptophan hydroxylase, the 5-HT-synthesizing enzyme. 2. Serotonergic neurons fired spontaneously (approximately 1 Hz), with maximal steady state firing rates of < 4 Hz. 5-Hydroxytryptamine caused hyperpolarization and cessation of spike activity in these neurons by activating inwardly rectifying K+ conductance via somatodendritic 5-HT1A receptors. 3. Unitary glutamatergic excitatory post-synaptic potentials (EPSP) and currents (EPSC) were evoked in serotonergic neurons by local electrical stimulation. Evoked EPSC were potently inhibited by 5-HT, an effect mediated by presynaptic 5-HT1B receptors. 4. In conclusion, serotonergic caudal raphe neurons are spontaneously active in vitro; they receive prominent glutamatergic synaptic inputs. 5-Hydroxytryptamine regulates serotonergic neuronal activity of the caudal raphe by decreasing spontaneous activity via somatodendritic 5-HT1A receptors and by inhibiting excitatory synaptic transmission onto these neurons via presynaptic 5-HT1B receptors. These local modulatory mechanisms provide multiple levels of feedback autoregulation of serotonergic raphe neurons by 5-HT.

Animals↗
PubMed2004

Neuromodulation of the locomotor network by dopamine in the isolated spinal cord of newborn rat.

We have analysed the action of the neuromodulatory catecholamine, dopamine (DA), on the lumbar locomotor network using an isolated in vitro newborn rat spinal cord preparation. We have also attempted to determine the respective contribution of the D1- and D2-like receptors on the dopamine-mediated effects. Bath application of DA-induced slow locomotor-like rhythmic activity (cycle-period 20-30 s) in ventral motor roots. Bursts were alternating between segmental right and left side and between ipsilateral flexor and extensor units. This rhythm was blocked by D1 (SCH-23390) and D2 (raclopride, sulpiride) receptor antagonists, but was unaffected by the dopamine-beta-hydroxylase blocker, fusaric acid, thereby ruling out indirect noradrenaline-mediated effects. The D1 agonist, SKF-81297 induced prolonged slow rhythmic bursting, while the selective D2 agonists, quinpirole and quinelorane, had no effect. DA and the D1 agonist, SKF-81297 also increased the period and burst amplitude of N-methyl-d-l-aspartate-induced locomotor activity. The effects of dopamine and SKF-81297 on the N-methyl-d-l-aspartate-induced rhythm were long-lasting; persisting for 1 hour after washout. The DA action was blocked by MDL-12 330 A, an inhibitor of adenylate cyclase, suggesting the involvement of cAMP. Together these results indicate that dopamine can exert neuromodulatory actions on mammalian motor networks via short-lasting permissive influences and a newly reported, long-lasting modulation of motor network activity.

Animals↗
PubMed1988

Muscarinic agonists evoke neurotransmitter release: possible roles for phosphatidyl inositol bisphosphate breakdown products in neuromodulation.

Carbachol (CCh), a muscarinic agonist that elicits the formation of inositol trisphosphate (IP3) and diacylglycerol (DG), induces a calcium-dependent [3H]norepinephrine ([3H]NE) release [IC50 = (2.7 +/- 0.5) X 10(-4) M] in rat brain slices. Similarly, other muscarinic agonists evoke [3H]NE release which is specifically inhibited by muscarinic antagonists such as 3-quinuclidinyl benzilate, atropine, and N-methyl-4-piperidyl benzilate. The atropine-sensitive evoked release is effectively inhibited by neomycin (IC50 = 50 microM), a phospholipase C inhibitor that interferes with IP3-dependent cellular processes. In addition, polymyxin B, a rather selective inhibitor of protein kinase C (PK-C), abolishes the agonist-mediated release with a half-maximal effective concentration of 0.53 microM (750 ng/ml). These results have a significant implication for the mechanism by which agonists generating IP3 and DG act as inducers of neurotransmitter release in the CNS. However, since both neomycin and polymyxin B act also as N-calcium-channel blockers, other possible mechanisms are discussed. The CCh-induced release suggests that in the CNS an agonist-receptor interaction leads to a calcium-dependent neurotransmitter release, most likely via promoting the IP3/DG as second messengers followed by activation of PK-C.

Animals↗
PubMed1988

Neuromodulator-mediated phosphorylation of specific proteins in a neurotumor hybrid cell line (NCB-20).

Mouse neuroblastoma X embryonic Chinese hamster brain explant hybrid cell line (NCB-20) forms functional synapses when intracellular cyclic AMP levels are elevated for a prolonged period of time. NCB-20 cells were labeled with [32P]orthophosphate under conditions where 2-chloroadenosine gave maximum increases of 32P incorporation into tyrosine hydroxylase in nerve growth factor dibutyryl cyclic AMP-differentiated PC12 (pheochromocytoma) cells. When NCB-20 cells were exposed to activators [5-hydroxytryptamine (5-HT), prostaglandin E1, or forskolin], resulting in activation of cyclic AMP-dependent protein kinase, increased 32P incorporation into two major proteins [130 kilodaltons (kDa) and 90 kDa] occurred. 5-HT (in the presence of phosphodiesterase inhibitor, isobutylmethylxanthine) gave a three- to fourfold increase, and forskolin a four- to sevenfold increase in 32P incorporation into the 90-kDa protein. [D-Ala2,D-Leu5]-enkephalin, which decreased cyclic AMP levels and reversed the 2-chloroadenosine-stimulated phosphorylation of tyrosine hydroxylase in differentiated PC12 cells, also reversed the stimulation of phosphorylation of the 90-kDa protein in NCB-20 cells. Pretreatment of NCB-20 cells with a calcium ionophore, A23187, gave increased phosphorylation of the 90- and 130-kDa proteins, but phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (tumor promoting agent), cell depolarization with high K+, or pretreatment with dibutyryl cyclic GMP had no effect on phosphorylation of these proteins. In contrast, phosphorylation of an 80-kDa protein was decreased by forskolin, but increased following activation of the calcium/phospholipid-dependent kinase with tumor promoting agent. Neither the 90-kDa nor the 80-kDa protein showed any immunological cross-reactivity with synapsin, a major synaptic protein known to be phosphorylated by cyclic AMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase, but not calcium/phospholipid-dependent protein kinase. This suggests that in NCB-20 cells, several unique proteins can be phosphorylated by cyclic AMP-dependent protein kinase in response to hormonal elevation of cyclic AMP levels. In contrast, an 80-kDa protein is the primary substrate for calcium/phospholipid-dependent protein kinase, and its phosphorylation is inhibited by agents that elevate cyclic AMP levels and thereby activate cyclic AMP-dependent protein kinase.

1-Methyl-3-isobutylxanthine↗
PubMed2004

The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite 'scavenger'?

Hydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown to stimulate N-methyl-D-aspartate (NMDA) receptors to enhance long-term potentiation suggesting a novel neuromodulatory role in vivo. Endogenous levels of H2S in the brain are reported to range between 10 and 160 microm. Considerably lower H2S levels are reported in the brains of Alzheimer's disease (AD) patients, where levels of brain protein nitration (probably mediated by peroxynitrite) are markedly increased. Activation of NMDA receptors leads to intracellular tyrosine nitration by peroxynitrite. Because H2S and peroxynitrite are important mediators in brain function and disease, we investigated the effects of the H2S 'donor', sodium hydrogen sulfide (NaSH) on peroxynitrite-mediated damage to biomolecules and to cultured human SH-SY5Y cells. H2S significantly inhibited peroxynitrite-mediated tyrosine nitration and inactivation of alpha1-antiproteinase to a similar extent to reduced glutathione at each concentration tested (30-250 microm). H2S also inhibited peroxynitrite-induced cytotoxicity, intracellular protein nitration and protein oxidation in human neuroblastoma SH-SY5Y cells. These data suggest that H2S has the potential to act as an inhibitor of peroxynitrite-mediated processes in vivo and that the potential antioxidant action of H2S deserves further study, given that extracellular GSH levels in the brain are very low.

Cell Line↗
PubMed2006

Age-related effects of the neuromodulator D-serine on neurotransmission and synaptic potentiation in the CA1 hippocampal area of the rat.

The effects of the co-agonist of the N-methyl-D-aspartate receptor (NMDAr) D-serine on glutamatergic neurotransmission and synaptic potentiation were studied in the CA1 hippocampal field of young (3-5 months old) and aged (25-27 months old) Sprague-Dawley rats using ex vivo extracellular electrophysiological recording techniques. Exogenous d-serine depressed fast neurotransmission mediated by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate subtype of glutamate receptors in young but not in aged rats by acting on inhibitory glycinergic interneurons. In contrast, D-serine dose-dependently enhanced NMDAr-mediated synaptic responses in both groups of animals, but with a larger magnitude in aged rats, thus preventing the age-related decrease in NMDAr activation. D-serine also increased the magnitude of long-term potentiation in aged but not in young rats. Finally, D-serine levels were dramatically reduced in hippocampal tissues of aged rats. Taken together, these results indicate a weaker activation of the NMDAr glycine modulatory site by endogenous D-serine in aged animals, which accounts for a reduced NMDAr contribution to synaptic plasticity in ageing.

Aging↗
PubMed1989

Angiotensin neuromodulation of adrenergic and purinergic co-transmission in the guinea-pig vas deferens.

1. The effects of angiotensin II (AII) and angiotensin III (AIII) on the isolated vas deferens of the guinea-pig were studied via three parameters: the overflow of adenosine 5'-triphosphate (ATP) and tritiated noradrenaline (NA), the mechanical response to field stimulation and the mechanical response to exogenous NA and alpha, beta-methylene ATP (alpha, beta-mATP). 2. At 2 Hz, AII enhanced the overflow of ATP and NA, whereas at 20 Hz, AII enhanced the overflow of NA but was without significant effect on ATP overflow. AIII, at 2 Hz, inhibited the overflow of ATP, but enhanced NA overflow, whereas at 20 Hz ATP overflow was unaffected, but NA overflow was still enhanced. 3. At 2 Hz, AII enhanced both phases of the response to field stimulation and at 20 Hz the overall response. AIII at 2 Hz enhanced the adrenergic response, but was without effect on the purinergic response to field stimulation. At 20 Hz, AIII was without effect on the overall response. 4. AII enhanced responses to exogenous NA and alpha, beta-mATP, whereas AIII was without effect. 5. These results provide evidence that both ATP and NA release are capable of being modulated by angiotensins. Furthermore, modulation of ATP release is frequency-dependent, whereas [3H]-NA release is not. These results raise questions about the mechanisms of storage and release of the sympathetic co-transmitters NA and ATP; they also show that angiotensin receptors in the guinea-pig vas deferens are not a homogeneous population.

Adenosine Triphosphate↗
PubMed2000

Self-sustaining status epilepticus: a condition maintained by potentiation of glutamate receptors and by plastic changes in substance P and other peptide neuromodulators.

We describe a model of self-sustaining status epilepticus (SSSE) induced by stimulation of the perforant path in free-running rats. In this model, seizures can be transiently suppressed by intrahippocampal injection of a blocker of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/ kainate synapses but return in the absence of further stimulation when the drug ceases to act. However, seizures are irreversibly abolished by blockers of N-methyl-D-aspartate receptors given locally or systemically. SSSE is enhanced by substance P and its agonists and blocked by its antagonists. SSSE induces novel expression of substance P-like immunoreactivity in hippocampal principal cells. These changes and those in other limbic peptides may contribute to the maintenance of SSSE and to the modulation of hippocampal excitability during epileptic seizures. NMDA

Age Factors↗