Modulatory effects of phosphatidylserine on the binding of muscarinic cholinergic receptor ligands

The modulation of the binding of muscarinic cholinergic receptor ligands by phosphatidylserine purified from bovine cerebral cortex (BC-PS) was examined in vitro and in vivo. The enrichment of bovine cerebral cortical synaptosomal membranes with BC-PS, using a fusion technique, produced a concentration-dependent decrease in the affinity (increase in K _d ) of [³H]quinuclidinyl benzylate (³H-QNB) specific binding to muscarinic acetylcholine receptors (mAChR), without changes in their maximal number (Bmax). Similar results were observed when [³H]oxotremorine (³H-OXO) was used to label a high affinity subpopulation of mAChR. On the other hand, preincubation of BC-PS liposomes with synaptosomal membranes in a nonoptimum fusion condition (at pH 7.4) did not alter the binding properties of both radioligands. Fusion experiments using a pure phosphatidylserine preparation from spinal cord revealed a similar decrement in the affinity of³H-QNB specific binding. Five day’s intraperitoneal (i.p.) administration of 15 mg/kg of BC-PS liposomes in rats increased the maximal number of cerebral cortical binding sites for³H-OXO. Scatchard analysis revealed no changes in the apparent dissociation constant. This modification is selective in relation to the neural structure studied. Thus, BC-PS treatment did not modify³H-OXO binding in the hippocampal formation and cerebellum. In contrast, parallel experiments using the muscarinic antagonist³H-QNB showed no alteration in the binding properties of mAChR. Five day’s i.p. administration of 15 mg/kg/d of phosphatidylcholine from bovine cerebral cortex (BC-PC) liposomes produced quite similar results to those obtained with BC-PS. These results indicate that mAChR are under the modulatory action of phosphatidylserine (PS) and phosphatidylcholine (PC), and suggest that this endogenous phospholipids may play a regulatory role on the mAChR. The possible implications of these findings on the effects of PC or PS treatment in neurological disorders involving a decrease in central cholinergic functions are discussed.     

Effects of morphine and naloxone on behaviour in the hot plate test: an ethopharmacological study in the rat

The objectives of this study were: i) to analyse the effects of morphine and naloxone on the rat's behaviour in the hot plate test using an ethological approach, and ii) to compare the effectiveness of repeated versus single test paradigms. Animals received either morphine (0, 3, 6 or 9 mg/kg SC) or naloxone (0, 0.01, 0.1 or 1 mg/kg SC). For repeated hot plate measures, rats were tested before and 60, 120, 180 and 240 min following morphine treatment, as well as 30, 60, 90 and 120 min after naloxone injection. For the single test schedule, rats were tested only once 60 min after morphine or 30 min after naloxone administration, or at 60, 120, 180, 240 and 300 min after 9 mg/kg morphine treatment. Behaviour was videotaped and analysed by an ethogram and ethological techniques. A cluster analysis revealed that the most frequently displayed patterns could be categorised into exploratory sniffing reactions (walk-sniff, immobile-sniff) and noxious-evoked elements, including primary (paw-licking, stamping), escape (jumping, leaning posture) and independent (hindleg-withdrawal) patterns. During repeated tests, morphine treatment induced: i) a maximum hypoalgesic effect 60 min post-injection (noxious-evoked patterns were significantly reduced), and ii) an unexpected thermal hyperreactivity rebound effect after 120 min (paw-licking and hindleg-withdrawal were enhanced), although changes in hindpaw-licking are more indicative of a hyperalgesic rebound effect. Most changes were quite similar during the single test schedule at 60 and 120 min after morphine injection. With regard to naloxone treatment, jumping latency was significantly decreased during the repeated test schedule, but not on single exposure to the plate. Other elements were facilitated, however, in the single test (stamping, leaning posture, hindleg-withdrawal). The results indicated that both repeated and single tests paradigms are of value for testing the effects of morphine and naloxone on rats. However, under our conditions the single test paradigm gave a better picture of the overall effects of the drug. Learning as well as habituation and sensitization may mask certain effects during repeated tests. In conclusion, an ethological analysis of the rat's behaviour in the hot plate test following administration of morphine and naloxone has been validated in this study.     

Emotion-related cerebral asymmetry: hemodynamics measured by functional ultrasound

This study assessed the use of transcranial Doppler ultrasound in detecting selective changes in cerebral blood flow velocity during emotional processes. The role of the respective hemispheres in emotional processing is controversial. Cerebral control of emotional processing has previously been investigated by analysis of patients with unilateral brain damage, experiments with selective stimulation of only one hemisphere, and more recently by imaging techniques measuring local cerebral blood flow. We investigated mean flow velocity continuously and simultaneously in both the right and left middle cerebral arteries (MCAs) in 16 healthy right-handed young subjects at rest and during the performance of three tasks: task 1: 15 slides with nonemotional content; task 2: 15 slides with negative emotional content; task 3: 15 slides with nonemotional content with different content from that in task 1. The three tasks produced significantly different effects on the right and left hemispheres. During the two nonemotional tasks the increase in mean flow velocity over basal values was similar in the two MCAs (task 1: left MCA = 3.27 ± 1.9%; right MCA = 3.63 ± 2.1%; task 3: left MCA = 2.42 ± 0.7%; right MCA = 2.56 ± 1.3%); the negative emotional task was accompanied by a significantly higher increase in the right (11.31 ± 1.6%) than in the left MCA (4.72 ± 3.7%; analysis of variance two-way interaction: side of recording x task, F = 43.6, P < 0.001). These results show the possibility of obtaining specific functional information from bilateral transcranial Doppler ultrasound and suggest the involvement of the right hemisphere in emotional processing. Received: 4 March 1999 Received in revised form: 29 June 1999 Accepted: 5 August 1999     

Vertical subcutaneous pedicle flaps for posterior perineal reconstruction

PURPOSE: Loss of a certain amount of cutaneous tissue of the perineal region may be remedied by first intention with creation of cutaneous flaps, thus preventing second intention healing. METHODS: We present three emblematic cases in which the posterior perineal region was reconstructed by means of vertical subcutaneous pedicle flaps, subsequent to cutaneous tissue loss after surgery for extensive condilomas or neoplastic pathologies. RESULTS: Tissue loss was repaired by means of a V-Y type vertical subcutaneous pedicle flap, constructed laterally of the extirpation zone and advanced in a median direction. In all cases, no ischemia or infection of flaps occurred; sphincteral continence and long-term aesthetic results have proved to be satisfactory. CONCLUSIONS: Vertical pedicle subcutaneous flaps are well vascularized, extremely mobile, and easy to perform and have no serious postoperative complications.     

Genetic markers in primary open-angle glaucoma

Purpose: To investigate possible associations between genetic markers and Primary Open-Angle Glaucoma (POAG). Methods: A number of genetic markers were typed in 84 unrelated patients with POAG and compared with a random sample of healthy individuals. The markers were Transferrin, Group Specific Component, G1m (1), G1m (2) and G3m (5) Allotypes, Adenylate Kinase, Adenosin Deaminase, Glyoxalase I and Acid Phosphatase and PCR-based markers HLA-DQA1 and D1S80. Results: No significant differences were found except the strong association between the group of POAG patients and Acid Phosphatase ACP^*C allele (² = 32.86; p < 0.0001). Conclusions: Since Acid Phosphatase gene is localized to chromosome 2p23, this result could be a first comprehensive step in the localization of POAG genes.     

Die anomalen Fusionsbewegungen: Der senso-motorische Aspekt des anomalen Binokularsehens

Zusammenfassung Es wurde nachgewiesen, daß bei konkomitierender Esotropie außer sensorischen Folgen auch senso-motorische Folgezustände vorkommen. Sie lassen sich vor allem mit Prismen nachweisen und werden als fusionsbedingt aufgefaßt (anomale Fusionsbewegungen).Bei 30 Patienten wurden die Eigenschaften dieser Vorgänge untersucht und erklärt. Schließlich wurde der Zusammenhang zwischen den anomalen Fusionsbewegungen und schon früher von anderen Autoren beschriebenen Krankheitsbildern analysiert, die je nach der ihnen zugrundegelegten Auffassung, unter verschiedenen Namen bekannt waren.

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Anomalous fusional movements: The sensorimotor aspect of anomalous binocular vision

Summary It has been demonstrated that, besides sensory adaptation phenomena, sensorimotor phenoma may also develop in concomitant esotropia. The existence of the latter entity can be shown particularly by means of prisms and is interpreted as fusional in origin. It is therefore defined as anomalous fusional movements.The features of these anomalous fusional movements were studied in a group of 30 patients, mainly in order to investigate their finality.Correlations were evaluated between anomalous fusional movements and entities previously described by different names according to the interpretation given them by various authors.

     

Partial Motor Epilepsy with "Negative Myoclonus"

Three children had both nocturnal unilateral motor seizures and daytime ipsilateral "negative myoclonus" which occurred so frequently that it resembled asterixis. Neurophysiologic studies demonstrated lateralized spike discharges that were time-locked to postural lapse in the contralateral outstretched arm. The clinical course was characterized by good seizure control with benzodiazepines.     

The importance of angiogenesis in ovarian cancer

Advanced stage ovarian cancer has a high rate of recurrence even after surgery followed by chemotherapy combining carboplatin and a taxane. New strategies are currently under way to combat this situation and one of the most promising ones is based on the knowledge that angiogenesis, the mechanism of formation of new blood vessels coupled with the degradation of the extracellular matrix for metalloproteinases, could be crucial in the development of this tumor. The principal molecule implicated in angiogenesis process of ovarian cancer is the vascular endothelial growth factor (VEGF). Several studies are now in progress to clarify its role as a diagnostic tool or its therapeutic implication. Presently, there is no indication for the use of VEGF in a preliminary diagnosis seeing that an increase in levels can be seen in both benign and malignant ovarian conditions. VEGF is also responsible for an increase in vascular permeability and is directly related to symptoms such as ascites and pleural effusion, both of which are frequent in ovarian cancer. Several papers have analised the role of VEGF as a prognostic factor and some of them do confirm VEGF as an independent prognostic factor in ovarian cancer. VEGF and the metalloproteinase system coupled with angiogenesis are currently being evaluated as therapeutic targets but no positive results have yet to be seen in this field.      

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.     

The wide clinical spectrum of nocturnal frontal lobe epilepsy

Nocturnal frontal lobe epilepsy (NFLE) has become clinically relevant in recent years. NFLE represents a spectrum of clinical manifestations, ranging from brief, stereotyped, sudden arousals, often recurring several times per night, sometimes with a quasi-periodic pattern, to more complex dystonic-dyskinetic seizures and to prolonged "somnambulic" behaviour. Episodes of increasing intensity have been labelled as paroxysmal arousal (PA), nocturnal paroxysmal dystonia (NPD) and episodic nocturnal wandering (ENW). NFLE affects both sexes with a higher prevalence for men, is frequently cryptogenetic and displays a strong familial trait for parasomnias and epilepsy (NFLE). Seizures appear more frequently between 14 and 20 years of age, but can affect any age and tend to increase in frequency during life. Interictal and ictal scalp electroencephalography (EEG) are often normal, the use of sphenoidal leads may be helpful. Carbamazepine taken at night is often effective at low doses, but a third of the patients are resistant to anti-epileptic drugs (AED) treatment. A familial form, characterized by an autosomal dominant transmission, has also been described. Autosomal dominant nocturnal frontal lobe epilepsy is a genetic variant of NFLE, in itself both clinically and biologically heterogeneous. NFLE should be suspected in the presence of frequent stereotyped paroxysmal nocturnal motor events arising or persisting into adulthood. Videopolysomnography is mandatory to confirm the diagnosis.