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PubMed2006

Estradiol inhibition of voltage-activated and gonadotropin-releasing hormone-induced currents in mouse gonadotrophs.

We report the first study of voltage-activated and GnRH-induced plasma membrane currents and their modulation by estradiol (E2) in mouse gonadotrophs. In consideration of the pleiotropic effects of E2 on gonadotrophin secretion and the relationship between plasma membrane electrical excitability and secretion, our objective was to determine the role of E2 in modulating gonadotroph plasma membrane currents. We measured total voltage-activated and GnRH-induced currents using the perforated-patch configuration of the patch-clamp technique, which preserves signaling pathways, including GnRH-induced Ca2+ oscillations. We show that female mouse gonadotrophs are similar to those from other species in that the voltage-activated net current response exhibits an inward fast activating current that is inhibited by tetrodotoxin, which is characteristic of a Na+ current, and a larger magnitude outward current with a profile suggesting the presence of multiple K+ currents. Furthermore, in voltage-clamped mouse gonadotrophs, GnRH activates large amplitude current oscillations that are apamin sensitive and have a reversal potential of -90 mV, consistent with Ca2+-activated K+ currents. Significantly, E2 pretreatment for 2-5 d decreased the density of both the peak outward voltage-activated current and the peak GnRH-induced current. The specific linkage between the observed E2 effects on membrane currents and, ultimately, gonadotroph function remains to be established. However, because decreased K+ current density is associated with an increase in membrane electrical excitability, we postulate increased excitability is one of the modes of action of E2 in sensitizing the gonadotroph to GnRH, an event central to the regulation of cyclic gonadotrophin secretion.

Animals↗
PubMed1994

Radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome.

OBJECTIVE: To report on the experience with radiofrequency catheter ablation of accessory atrioventricular pathways in patients with Wolff-Parkinson-White syndrome in terms of the duration of fluoroscopy exposure to the patient and the operator and the effect of accessory-pathway location and operator experience on the success rate. DESIGN: Retrospective review. SETTING: Tertiary care university hospital. PATIENTS: Two hundred consecutive patients with Wolff-Parkinson-White syndrome who underwent radiofrequency catheter ablation between September 1990 and June 1992. INTERVENTIONS: Electrophysiologic study and radiofrequency catheter ablation. MAIN OUTCOME MEASURES: Success rate, duration of fluoroscopy, complications and long-term follow-up. RESULTS: Of the 224 accessory pathways in the 200 patients 135 were left free wall, 47 posteroseptal, 32 right free wall and 10 anteroseptal. The overall success rate increased from 53% in the first 3 months of the study period to 96% in the last 3 months. The success rate depended on the location of the accessory pathway. The duration of fluoroscopic exposure decreased from 50 (standard deviation [SD] 21) minutes in the first 3 months to 40 (SD 15) minutes in the last 3 months (p < 0.05). Complications occurred in 3.5% of the patients; they included hemopericardium, cerebral embolism, perforation of the right atrial wall, air embolism in a coronary artery and hematoma at the arterial perforation site. None of the complications resulted in death. CONCLUSIONS: With experience, radiofrequency catheter ablation of accessory pathways can have an overall success rate of more than 95% and a complication rate of less than 4%. Such rates make this procedure suitable for first-line therapy for patients with Wolff-Parkinson-White syndrome.

Adolescent↗
PubMed1992

Normal anatomy and neurophysiology of the hippocampal formation.

This article reviews the anatomy and neurophysiology of the normal hippocampal formation, with emphasis on the human hippocampus. The hippocampus receives inputs from numerous limbic, cortical, and subcortical areas, primarily via the entorhinal cortex and subiculum. The primary pathway of neural activity entering the hippocampus is from entorhinal cortex via the perforant path to the dentate granule cells, with collaterals to CA1 and CA3 pyramidal cells. Mossy fibers from granule cells excite CA3 pyramidal cells and hilar interneurons. CA3 pyramidal cells excite CA1 pyramidal cells, with local and commissural excitatory collaterals exciting other CA3 pyramidal cells and septum. CA1 pyramidal cells send efferent fibers to subiculum, entorhinal cortex, and several subcortical areas. The principal excitatory synapses are glutamatergic, with two important postsynaptic receptor types, alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid and N-methyl-D-aspartate. The primary inhibitory transmitter is gamma-aminobutyric acid (GABA), with two postsynaptic receptor types, GABAA and GABAB. A number of modulatory transmitters and neuropeptides are also present. Inhibitory local synaptic networks in the hippocampus are described. Membrane ion channels in hippocampal neurons, particularly Ca2+ channels and K+ channels, are responsible for the regulation and patterning of neural activity. Long-term potentiation and axon sprouting are two experimental paradigms of neural plasticity presumably involved in hippocampal memory function.

Animals↗
PubMed1983

Partial kindling and emotional bias in the cat: lasting aftereffects of partial kindling of the ventral hippocampus. II. Physiological changes.

The first study revealed that evocation of repeated afterdischarges (ADs) in the perforant path-dentate system of the ventral hippocampus of cats induced a lasting increase in defensive sensitivity to species-characteristic threats. This study examined interictally maintained changes in physiological properties of two limbic pathways which covaried with the behavioral changes. It was found that ADs which spread to the amygdala and ventromedial hypothalamus induced a lasting (30-60 days) increase in evoked transmission of excitatory activity from the amygdala to the ventromedial hypothalamus. This change is consistent with the role of the amygdalo-hypothalamic pathway in defensive behavior in the cat. Lasting increases in the EPSP component of the dentate field potential induced by perforant path stimulation were found, as well. Countering this increase in hippocampal excitability were long-lasting increases in recurrent inhibition. The increase in recurrent inhibition in the hippocampus was interpreted to mean that the ability of the hippocampus to transmit neural activity at high rates was lastingly impaired. This finding is also consistent with the proposed role of the ventral hippocampus in modulating predatory aggression and defense. It was concluded that interictally maintained changes in defensiveness were dependent on a form of lasting synaptic potentiation of excitatory activity from the amygdala to the ventromedial hypothalamus, and an equally lasting attenuation of function due to increased recurrent inhibition in the ventral hippocampus.

Aggression↗
PubMed1996

Duplex scanning for recurrent varicose veins.

BACKGROUND: Most studies of recurrent varicose veins have been based on the findings clinically, at operation, or on phlebography. Occasionally these findings have been compared with Doppler findings produced by hand-held continuous-wave Doppler. Duplex scanning is a more refined approach to the assessment of recurrent varicose veins. METHODS: 202 patients (267 legs) have been examined consecutively for recurrent varicose veins between January 1990 and December 1995 at St George Vascular Laboratory. This was a retrospective study of some aspects and patterns of recurrence of varicose veins in this group. RESULTS: The ratio of female to male was 3:1. The mean age of the group was 52 years and mean time to recurrence was 13 years (1 year 95% CI). There were six patterns of recurrence accounting for 95.2% of legs. In descending order of frequency, these were: (i) the saphenofemoral junction and long saphenous vein were intact and incompetent (44.6%); (ii) an incompetent thigh perforator and long saphenous vein remained intact; there was no saphenofemoral junction (16.5%); (iii) the long saphenous vein remained intact and incompetent; there was no saphenofemoral junction (10.5%); (iv) there was an incompetent saphenofemoral junction only (9.74%); (v) there was an intact and incompetent saphenopopliteal junction alone (9.74%); and (vi) an isolated thigh perforator was incompetent, with no more proximal site of incompetence detected (4.12%). Incompetent calf perforator (69.2%) and gastrocnemius veins (9.3%) were frequently detected, but rarely existed in isolation (seven legs in total). CONCLUSIONS: Duplex scanning is an important recent adjunct to the management of recurrent varicose veins in order to define the pathway of incompetence'. The saphenofemoral junction and long saphenous vein remain the key to recurrence of varicose veins. Calf perforator and gastrocnemius vein incompetence are of secondary importance in recurrent varicose veins.

Female↗
PubMedDate not supplied

Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression.

All synaptically-based neuropsychological theories of learning postulate that there are changes resulting from neural activity which are long-lasting and confined to specific sets of synapses. In the past decade a form of synaptic strengthening known as long-term potentiation (LTP) has been found which results from high-frequency neural activity and is of sufficient duration to model as a learning mechanism. Some early tests of the synaptic specificity of LTP in area CA1 of the hippocampus indicated that although LTP was specific to the tetanized pathway, in a converging untetanized pathway it was associated with depression of synaptic transmission lasting for at least 30 min. However, others have found that this heterosynaptic depression more usually decays within 5-15 min post-tetanus despite the maintenance of LTP in the tetanized pathway. Similarly, in the dentate gyrus (DG), LTP of either the lateral (LPP) or medial (MPP) components of the perforant path afferents has been associated with only short-lasting reciprocal heterosynaptic depression. Here, using more detailed measurement of stimulus intensity curves, we report that tetanization of either MPP or LPP reliably depresses synaptic transmission in the other pathway for at least 3 h. This heterosynaptic depression, considerably smaller than the usual magnitude of LTP, was obtained regardless of whether LTP had been produced in the tetanized homosynaptic pathway. Heterosynaptic long-term depression was not observed if the test pathway had been previously tetanized.

Animals↗
PubMed2001

Crohn's disease in a patient with acute spinal cord injury: a case report of diagnostic challenges in the rehabilitation setting.

Diagnosis of the abdominal emergency in tetraplegic and high paraplegic patients remains challenging. Classic peritoneal signs, such as a rigid abdomen, rebounding, guarding, and Murphy's sign may be absent, whereas subtle physical, laboratory, or radiologic abnormalities may be the only evidence for an acute abdomen. Our report describes the course of a 70-year-old man with C5 American Spinal Injury Association class A tetraplegia who developed a perforated cecum secondary to Crohn's disease. We review the visceral and somatic sensory pathways for abdominal pain with emphasis on the challenges in assessing the acute abdomen in a patient with spinal cord injury (SCI). Recommendations for the assessment of the acute abdomen in an individual with SCI will be provided. This is the first reported case of Crohn's disease in an individual with an acute SCI. It shows the importance of maintaining high clinical suspicion for unexpected intraabdominal processes that may lead to significant morbidity and mortality if left undiagnosed.

Accidents, Traffic↗
PubMed1997

The effects of sevoflurane on population spikes in CA1 and dentate gyrus of the rat hippocampus in vitro.

UNLABELLED: We studied the effects of sevoflurane on population spikes (PSs) in two synaptic pathways in rat hippocampal slices. Stimulating electrodes were placed on Schaffer collateral fibers or perforant path to activate inputs to CA1 pyramidal neurons or dentate gyrus (DG) neurons, respectively. Extracellular glass microelectrodes were used to record PSs. The paired-pulse stimulus was used to induce the paired-pulse facilitation (PPF). Sevoflurane (0.4-5.0 vol%) significantly decreased the amplitudes of PSs of CA1 and DG in a dose-dependent and reversible manner (25% effective dose values were 4.1 and 0.9 vol%, respectively). The stimulus-response relationships for PS amplitudes revealed that sevoflurane increased the threshold for PS generation in CA1 and DG. Sevoflurane (2.0 vol%) significantly enhanced PPF from 127% and 263% to 153% and 494% in CA1 and DG, respectively. The results imply that the effects of sevoflurane on PSs are greater in DG than in CA1 neurons, that sevoflurane enhances the PPF in both CA1 and DG, and that the actions of sevoflurane are not similar to those of other volatile or intravenous anesthetics previously reported in hippocampal preparations. IMPLICATIONS: The volatile anesthetic sevoflurane alters neural excitability of individual pathways in the hippocampus in a manner different from other general anesthetics. The results are consistent with a site-specific mechanism of action for general anesthesia.

Anesthetics, Inhalation↗
PubMed2001

Differential effect of TEA on long-term synaptic modification in hippocampal CA1 and dentate gyrus in vitro.

The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni2+ (50 microM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni2+ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 microM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni2+. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni2+. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.

2-Amino-5-phosphonovalerate↗
PubMed2003

Duplex ultrasound evaluation of lower extremity venous insufficiency.

Physicians unfamiliar with venous insufficiency, particularly disorders of the superficial venous system, often underestimate the complexity of the problem and the importance of proper evaluation before initiating treatment. In addition to a directed history evaluation and physical examination, additional evaluation with use of a variety of noninvasive diagnostic instruments, including duplex ultrasound, may be necessary when determining the cause, severity, and best treatment options available for a particular patient. After such evaluation, the treating physician should have a precise map of the patient's pathways of venous insufficiency, including sources of reflux (eg, saphenofemoral junction, saphenopopliteal junction, perforators), tributaries, vein size, and vein morphology.

Humans↗
PubMed2001

Observations on the feeding behaviour of Paratrichodorus anemones in relation to tobravirus transmission.

Feeding by P. anemones, an efficient vector of tobacco rattle virus (TRV), was investigated by video-enhanced interference light microscopy. Four stages were observed after transfer of individual nematodes, extracted from soil, to Nicotiana tabacum seedling roots in agar: i) acclimatisation; ii) approach and scrutiny; iii) preparation; and iv) feeding. Prior to commencement of stage 'iv' about 4 cells perforated by rapid onchiostyle thrusting remained alive, each having been almost immediately abandoned by the nematode. During the stage iv) approximately 5% of perforated cells remained alive. Feeding on individual cells was similar to that previously reported for Trichodorus similis: cells from which cytoplasm was ingested after a prolonged period of salivation were invariably killed, with adjacent cells being unaffected. During feeding a number of cells perforated but soon afterwards abandoned by P. anemones remained alive, providing an effective pathway for successful transmission of TRV to plants by the nematode.

Animals↗
PubMed2001

Translocon pores in the endoplasmic reticulum are permeable to a neutral, polar molecule.

The pore of the translocon complex in the endoplasmic reticulum (ER) is large enough to be permeated by small molecules, but it is generally believed that permeation is prevented by a barrier at the luminal end of the pore. We tested the hypothesis that 4-methylumbelliferyl alpha-d-glucopyranoside (4MalphaG), a small, neutral dye molecule, cannot permeate an empty translocon pore by measuring its activation by an ER resident alpha-glucosidase, which is dependent on entry into the ER. The basal entry of dye into the ER of broken Chinese hamster ovary-S cells was remarkably high, and it was increased by the addition of puromycin, which purges translocon pores of nascent polypeptides, creating additional empty pores. The basal and puromycin-dependent entries of 4MalphaG were mediated by a common, salt-sensitive pathway that was partially blocked by spermine. A similar activation of 4MalphaG was observed in nystatin-perforated cells, indicating that the entry of 4MalphaG into the ER did not result simply from the loss of cytosolic factors in broken cells. We reject the hypothesis and conclude that a small, neutral molecule can permeate the empty pore of a translocon complex, and we propose that translationally inactive, ribosome-bound translocons could provide a pathway for small molecules to cross the ER membrane.

Animals↗
PubMed1990

Electrical ablation of posteroseptal accessory pathways.

Electrical ablation of a posteroseptal accessory pathway by delivery of direct current electrical energy at the coronary sinus ostium was attempted in six patients. As a result of 12 procedures in these six patients, the posteroseptal accessory pathway was successfully ablated in one patient. Retrograde conduction only was affected in a further three patients, abolishing paroxysmal supraventricular tachycardia in two and reducing the tachycardia rate in one. One of the six patients developed coronary sinus perforation requiring prompt pericardial aspiration. The procedure is complicated, time consuming, of limited efficacy and coronary sinus perforation is a significant risk. Surgery remains the preferred option as a curative procedure for arrhythmias due to posteroseptal accessory pathway.

Adult↗
PubMed1993

[Results of surgical treatment in supraventricular tachycardias].

From May 1989 to May 1992, 44 patients (mean age 41 years, range 15-66) underwent surgery for supraventricular tachycardias: in 35 patients with atrioventricular reentrant tachycardia or atrial fibrillation associated with accessory pathway and refractory to medical treatment, the epicardial approach was used; in 8 with atrioventricular nodal reentrant tachycardia, a perinodal cryosurgery of the atrioventricular node was used, and in 1 patient with atrial flutter a cryosurgical ablation around the orifice of the coronary sinus and surrounding tissues was performed. All 38 accessory pathways were successfully ablated in 35 patients and no recurrences of delta wave or tachycardia were observed during a mean follow-up of 17 +/- 10 months. Atrial perforation during surgery and pericarditis were the only complications observed. All 8 patients with atrioventricular nodal reentrant tachycardia were successfully treated: in 2 patients dual pathways persisted after surgery but tachycardia was no longer inducible. No recurrences were observed during a mean follow-up of 15 +/- 4 months. Since surgery (15 months), the patient with atrial flutter has been free of recurrent episodes of atrial flutter. In conclusion, surgical treatment of supraventricular tachycardias is highly successful, with no mortality and very low morbidity. Should transcatheter ablation fail, surgery should be the treatment of choice in patients with frequent and symptomatic supraventricular tachycardias.

Adolescent↗
PubMed2006

Activation of the cGMP/PKG pathway inhibits electrical activity in rabbit urethral interstitial cells of Cajal by reducing the spatial spread of Ca2+ waves.

In the present study we used a combination of patch clamping and fast confocal Ca2+ imaging to examine the effects of activators of the nitric oxide (NO)/cGMP pathway on pacemaker activity in freshly dispersed ICC from the rabbit urethra, using the amphotericin B perforated patch configuration of the patch-clamp technique. The nitric oxide donor, DEA-NO, the soluble guanylyl cyclase activator YC-1 and the membrane-permeant analogue of cGMP, 8-Br-cGMP inhibited spontaneous transient depolarizations (STDs) and spontaneous transient inward currents (STICs) recorded under current-clamp and voltage-clamp conditions, respectively. Caffeine-evoked Cl- currents were unaltered in the presence of SP-8-Br-PET-cGMPs, suggesting that activation of the cGMP/PKG pathway does not block Cl- channels directly or interfere with Ca2+ release via ryanodine receptors (RyR). However, noradrenaline-evoked Cl- currents were attenuated by SP-8-Br-PET-cGMPs, suggesting that activation of cGMP-dependent protein kinase (PKG) may modulate release of Ca2+ via IP3 receptors (IP3R). When urethral interstitial cells (ICC) were loaded with Fluo4-AM (2 microm), and viewed with a confocal microscope, they fired regular propagating Ca2+ waves, which originated in one or more regions of the cell. Application of DEA-NO or other activators of the cGMP/PKG pathway did not significantly affect the oscillation frequency of these cells, but did significantly reduce their spatial spread. These effects were mimicked by the IP3R blocker, 2-APB (100 microm). These data suggest that NO donors and activators of the cGMP pathway inhibit electrical activity of urethral ICC by reducing the spatial spread of Ca2+ waves, rather than decreasing wave frequency.

Action Potentials↗
PubMed1978

Alternate pathway activation of complement in a Proteus mirabilis ulceration of the cornea.

A 63-year-old patient had an extensive infiltration, ulceration, and eventual perforation of the cornea caused by Proteus mirabilis. Histopathological examination of corneal tissue that was obtained at keratoplasty disclosed that the stroma was ulcerated with a diffuse infiltration of polymorphonuclear leukocytes. Immunopathological examination of the cornea revealed prominent and diffuse staining for properdin and C3 complement. There was an absence of staining for IgG, IgA, IgM, IgE, and C4 complement. These findings suggest that the alternate pathway of complement was activated in this ulcerated cornea and that immunopathological phenomena contribute to the polymorphonuclear infiltration found with Gram-negative ulcerations of the human cornea.

Complement C3↗