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At least 487 records · Page 27Linked to original sources
PubMed2005

Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease.

Intermittent stimulation of striatal dopaminergic receptors seems to contribute to motor dysfunction in advanced Parkinson's disease (PD). With severe dopaminergic denervation, exogenous levodopa is largely decarboxylated to dopamine in serotonergic terminals. If 5-HT1A autoreceptors regulate dopamine as well as serotonin release, in parkinsonian patients inhibition of striatal serotonergic neuron firing might help maintain more physiological intrasynaptic dopamine concentrations and thus ameliorate motor fluctuations and dyskinesias. To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study. Sarizotan alone or with intravenous levodopa had no effect on parkinsonian severity. But at safe and tolerable doses, sarizotan coadministration reduced levodopa-induced dyskinesias and prolonged its antiparkinsonian response (P < or = 0.05). Under the conditions of this study, our findings suggest that 5-HT1A receptor stimulation in levodopa-treated parkinsonian patients can modulate striatal dopaminergic function and that 5-HT1A agonists may be useful as levodopa adjuvants in the treatment of PD.

Aged↗
PubMed1975

Cycloheximide resistance in Chinese hamster cells. I. Spontaneous mutagenesis.

Resistance to cycloheximide (CHM) was studied in cultured Chinese hamster cells. Concentrations of CHM above 5-10-7 M were toxic for the cells. At concentrations above 9-10-7 M no colonies were recovered in selective medium. 15 resistant clones of independent origin were isolated in selective medium containing 7-10-7 M CHM. Resistance was stable when the cells were cultured under non-selective conditions. The spontaneous mutation rate was determined by the fluctuation test. Mutations to CHM resistance arose spontaneously. The spontaneous mutation rate to CHM resistance was about 10-5.

Animals↗
PubMed2005

Munc18-dependent regulation of synaptic vesicle exocytosis by syntaxin-1A in hippocampal neurons.

The fusion of secretory vesicles with the plasma membrane requires the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes between the vesicle-SNARE vesicle-associated membrane protein present on the vesicular membrane and the target-SNAREs SNAP-25 and syntaxin-1A. Syntaxin-1A fluctuates between an open and closed form allowing it to selectively bind to different biological effectors in different conformations. In the open form, it can participate in SNARE complex formation, however, in the closed form it negatively regulates N- and P/Q-type voltage-dependent calcium channels, and is capable of inhibiting calcium influx. Thus paradoxically, syntaxin appears to have both positive and negative roles in controlling calcium-driven synaptic vesicle fusion at synaptic terminals. We show here that overexpression of syntaxin-1A inhibited exocytosis, in a manner that could be rescued by either elevating or reducing external calcium, or increasing action potential firing frequency. Elevating the level of Munc18 by coexpression with syntaxin-1A also abolished this inhibition, suggesting that Munc18 serves to limit the negative regulatory role of syntaxin by binding to, and thereby buffering, its closed form. Our results also indicate that syntaxin can control the frequency-response characteristics of the presynaptic fusion machinery.

Animals↗
PubMed2003

Effect of acute and chronic administration of U50,488, a kappa opioid receptor agonist, in 6-OHDA-lesioned rats chronically treated with levodopa.

To evaluate the possible involvement of kappa opioid receptor-mediated mechanisms in levodopa-induced motor fluctuations, we have investigated the effects of U50,488, a selective kappa opioid agonist, on levodopa-induced motor alterations in rats with unilateral 6-OHDA lesion. Acute and chronic administration of U50,488 has been studied to evaluate the possible reversion or prevention of these levodopa effects. In a first set of experiments, rats were treated with levodopa (25 mg/kg with benserazide, twice daily, ip) for 22 days and, on Day 23 U50,488 (0.5, 1, or 3 mg/kg, i.p.) was administered immediately before levodopa. In a second set of experiments, rats were treated daily for 22 days with levodopa and U50,488 (1 or 3 mg/kg/day, i.p.). The duration of the rotational behavior induced by chronic levodopa decreased after 22 days (P < 0.05). Acute administration of U50,488 on Day 23 reversed this effect when low doses were administered (P < 0.05). Chronic U50,488 administration did not prevent the shortening in response duration induced by levodopa. Our results demonstrate that the kappa opioid receptor agonist U50,488 reverses but does not prevents levodopa-induced motor alterations in parkinsonian rats. These results suggest a role for kappa opioid receptor-mediated mechanisms in the pathophysiology of levodopa-induced motor response complications. These findings suggest that the stimulation of kappa opioid receptors might confer clinical benefit to parkinsonian patients under levodopa therapy suffering from motor complication syndrome.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2003

Neural mechanisms of transient and sustained cognitive control during task switching.

A hybrid blocked and event-related functional magnetic resonance imaging (fMRI) study decomposed brain activity during task switching into sustained and transient components. Contrasting task-switching blocks against single-task blocks revealed sustained activation in right anterior prefrontal cortex (PFC). Contrasting task-switch trials against task-repeat and single-task trials revealed activation in left lateral PFC and left superior parietal cortex. In both sets of regions, activation dynamics were strongly modulated by trial-by-trial fluctuations in response speed. In addition, right anterior PFC activity selectively covaried with the magnitude of mixing cost (i.e., task-repeat versus single-task trial performance), and left superior parietal activity selectively covaried with the magnitude of the switching cost (i.e., task-switch versus task-repeat trial performance). These results indicate a functional double dissociation in brain regions supporting different components of cognitive control during task switching and suggest that both sustained and transient control processes mediate the behavioral performance costs of task switching.

Adult↗
PubMed1989

Selective electrochemical biosensors from state-switching of bilayer and monolayer lipid membranes by lectin-polysaccharide complexes.

Interaction of the lectin concanavalin A with the polysaccharide glycogen can provide rapid spontaneous transients of the surface potential at bilayer and monolayer lipid membranes. The selective binding process can cause large, rapid potassium ion current fluctuations across bilayer membranes in a manner that is periodic and reproducible. The frequency of these transient ion current signals was shown to be related to sub-nanomolar concentrations of the reactive agents in aqueous solution. The physical mechanism responsible for ion current modulation was investigated by fluorescence methods using lipid vesicles, by the thermal dependence of the potassium ion current across planar bilayers and by pressure-area and dipolar potential measurements of lipid monolayers at an air-water interface. The mechanism is primarily associated with physical perturbations of lipid membranes by lectin-polysaccharide aggregates, resulting in the formation of localised domains of variable electrostatic potential and conductivity.

Biosensing Techniques↗
PubMed1999

Influence of endogenous progesterone on alprazolam pharmacodynamics.

The results of a recently completed study demonstrated that postmenopausal women were more sensitive to triazolam-induced psychomotor performance impairment when progesterone was administered concomitantly. That clinical evidence agrees with the emerging in vitro information regarding the rapid membrane effects of a progesterone metabolite that positively modulates the gamma-aminobutyric acid-A-benzodiazepine receptor complex. The objective of this study in premenopausal women was to determine whether the response to a benzodiazepine is altered when endogenous progesterone concentrations are high (luteal phases of a menstrual cycle) compared with when progesterone concentrations are low (follicular phases of a menstrual cycle). The pharmacokinetics and pharmacodynamics of oral alprazolam were evaluated in twelve healthy, normally menstruating women who were not receiving oral contraceptive agents. On two separate occasions, once during each phase of the menstrual cycle, the women randomly received an oral alprazolam 2-mg dose. Blood samples were collected, and psychomotor performance tests were conducted at selected times before and after dosing. These data show that fluctuations of endogenous progesterone across the menstrual cycle do not influence alprazolam pharmacodynamics. Despite endogenous progesterone concentrations being significantly higher during the midluteal than during the midfollicular drug administrations, no differences were observed in either the digit-symbol substitution test, card sorting by suit, or sedation scores on these two occasions. No pharmacokinetic differences were observed between the two menstrual cycle-phase drug administrations. In conclusion, the lack of changes during the menstrual cycle in demonstrable cognitive impairment and pharmacokinetics after alprazolam administration is reassuring. This implies that a dose adjustment made on the basis of menstrual timing is not required.

Adult↗
PubMed2004

Small effective population sizes in a widespread selfing species, Lymnaea truncatula (Gastropoda: Pulmonata).

We present here a spatial and temporal population genetic survey of a common freshwater snail, also a predominantly selfing species, Lymnaea truncatula. The rate of genetic diversity loss was quantified by estimating the effective size (Ne) of the snail populations, using two different methods. A temporal survey allowed estimation of a variance effective size of the populations, and a spatial survey allowed the estimation of an inbreeding effective size, from two-locus identity disequilibria estimates. Both methods were consistent and provided low Ne values. Drift due to (i) high amounts of selfing and (ii) fluctuations in population sizes because of temporary habitats, and also selection coupled to genome-wide linkage disequilibria, could explain such reductions in Ne. The loss of genetic diversity appears to be counterbalanced only very partially by low apparent rates of gene flow.

Analysis of Variance↗
PubMed1986

Detection cues in forward masking and their relationship to off-frequency listening.

Conventional and restricted-listening psychophysical tuning curve paradigms were used to evaluate the masking ability of forward maskers of different envelope characteristics, and the relationship between off-frequency listening effects and the envelope characteristics of both the variable masker and stationary masker used to restrict listening to a narrow region surrounding the probe. Maskers were selected so as to differ widely in the degree of fluctuation in their envelopes. The masker with the largest amplitude fluctuations exhibited greater forward-masking ability than other stimuli; this effect was observed on the high-frequency branch and within the tip region of the tuning curve. It is suggested that differences in masking ability may reflect the use of different signal detection cues. The results are also consistent with previous reports [D. Johnson-Davies and R.D. Patterson, J. Acoust. Soc. Am. 65, 756-770 (1979); B.J. O'Loughlin and B.C.J. Moore, J. Acoust. Soc. Am. 69, 1119-1125 (1981a)] which suggest that off-frequency listening is a factor contributing to the sharpness of psychophysical tuning curves. This effect is largely dependent, however, on the envelope characteristics of both variable and stationary maskers.

Adult↗
PubMed1996

Reproductive and developmental effects of disinfection by-products in drinking water.

Recent epidemiologic studies have reported associations between the consumption of chlorinated drinking water and reproductive and developmental effects. Here we review the available epidemiologic data, assess the hazard potential posed by exposure to disinfection by-products, identify critical data gaps, and offer recommendations for further research. The epidemiologic evidence supporting associations between exposure to water disinfection by-products (DBPs) and adverse pregnancy outcomes is sparse, and positive findings should be interpreted cautiously. The methods used during the early stages of research in this area have been diverse. Variability in exposure assessment and endpoints makes it difficult to synthesize or combine the available data. Exposure misclassification and unmeasured confounding may have lead to bias in risk estimation. Future studies of reproductive outcome and exposure to chlorinated water should use improved methods for exposure assessment to 1) assure selection of appropriate exposure markers, 2) assess seasonal and annual fluctuations in DBPs, 3) assess variability within the distribution system, and 4) assess exposure through multiple routes such as bathing and showering, as well as consumption. Population-based studies should be conducted to evaluate male and female fertility, conception delay, growth retardation, and specific birth defects. The reproductive and developmental effects of exposure to DBPs could be efficiently explored in ongoing investigations by incorporating valid exposure markers and relevant questionnaire information. Future studies should make use of naturally occurring variability in the concentrations of DBPs and may incorporate biomarkers of exposure and effect in their design. Epidemiologic investigations should be conducted in parallel with laboratory-based and animal studies in a coordinated, multidisciplinary approach.

Abnormalities, Drug-Induced↗
PubMed2005

Temporal statistics of the beam-wander contribution to scintillation in ground-to-satellite optical links: an analytical approach.

The beam-wander contribution to the scintillation in a ground-to-satellite free-space optical link is one of major importance. An analytical model, based on the duality between beam wander and angle-of-arrival fluctuations, is proposed for the temporal statistics. The expression of the probability density function of the log-amplitude fluctuations is first obtained. Then, the expressions of the spatial and temporal autocovariances are also obtained. We present plots of the beam-wander contribution to the log-amplitude variance, as a function of the transmitter aperture size and the turbulence accumulated in the propagation path. We also present the angular fluctuation and log-amplitude scintillation spectrum plots for some selected cases.

Journal Article↗
PubMed1993

[Laryngeal control mechanisms during respiration and phonation analyzed by excitability changes of laryngeal motoneurons in decerebrate cats].

Laryngeal motoneurons (LMNs) innervating the intrinsic laryngeal muscles also control glottal movements such as swallowing, respiration and phonation. The present study was performed on decerebrate cats to clarify the laryngeal control mechanisms during respiration and phonation using extracellular single unit recordings from the nucleus ambiguus. First, functional differences among LMNs during the respiratory phases were investigated by analysis of the activity of LMNs innervating laryngeal adductor (TA-LCA: thyroarytenoid-lateral cricoarytenoid) or abductor (PCA: posterior cricoarytenoid) muscles; Second, laryngeal control mechanisms during phonation were investigated by the analysis of neural activity of TA-LCA motoneurons during vocal fold vibration elicited by a constant air flow through the glottis. In both cases, motoneuronal excitability changes were expressed by measuring fluctuation of peak latencies of action potentials antidromically elicited by selective stimulation of the recurrent nerve or its peripheral branch. In 14 out of 24 TA-LCA motoneurons, neuronal excitability was increased during the expiratory phase, whereas in the remaining 10, it was increased during the later half of the inspiratory and the early half of the expiratory phase. On the other hand, 9 out of 13 PCA motoneurons showed increased neuronal excitability during the end of the expiratory and the beginning of the inspiratory phase, while the remaining 4 showed increased excitability during the inspiratory phase. These results suggest that there are functional differences among the homogeneous laryngeal motoneurons. In seven TA-LCA motoneurons, neuronal excitability was decreased by vocal fold vibration elicited by phonation throughout the whole respiratory cycle. On the other hand, when the bilateral superior laryngeal nerves were cut, neuronal excitability was increased during phonation throughout the whole respiratory cycle. These results indicate that TA-LCA motoneurons receive inhibitory inputs from the superior laryngeal nerve and excitatory inputs from the recurrent laryngeal nerve during the vocal fold vibration elicited by phonation.

Animals↗
PubMed1999

The effects of infant mortality on fertility revisited: new evidence from Latin America.

In this paper, we examine empirical evidence for a relation between infant and child mortality and fertility in Latin American countries from 1920 to 1990. We investigate the relation at several levels of aggregation and evaluate the extent to which evidence at one level is consistent with evidence at other levels. We first examine aggregate cross-country information over several decades, a type of data typically used in past research on the topic. We also examine yearly series of births, deaths, infant deaths, and socioeconomic indicators for selected countries to track the association between short-term fluctuations in fertility and infant mortality. Finally, we use micro-level data from the Demographic and Health Surveys (DHS) to assess the relation between fertility and child mortality from individual reproductive histories. The evidence we assemble from these different data sets is remarkably consistent and suggests small positive effects of infant mortality on fertility. These effects, however, may be too small to support the hypothesis that changes in child mortality are of more than modest importance in the process of fertility decline in Latin America in the late twentieth century.

Adult↗
PubMedDate not supplied

[The treatment of intradural arteriovenous fistulas in the spine: two case reports].

INTRODUCTION: Spinal dural arteriovenous fistulas (AVFs) frequently cause progressive myelopathy. Although endovascular approaches to spinal cord vascular malformations become an important adjunct or primary treatment of theses disorders, surgery can be safely performing in some categories. CASE REPORTS: Two males patients presented with progressively myelopathy two months and three years before, were diagnosed by typical MRI findings and spinal selective arteriograms of dorsal AVFs with single feeder of Spetzler's modified classification of spinal cord vascular lesions. After an attempt of embolization following diagnostic angiography in first case, surgical approach for clipping the afferent single feeder was done for both. CONCLUSIONS: Early recognition by selective diagnostic spinal angiography in patients with slowly progressive and fluctuating myelopathy, allow us surgery as recommended treatment in AVFs, so can effect a better outcome and often reverse presenting neurologic deficits.

Angiography↗
PubMed1988

AMPA, kainate, and quisqualate activate a common receptor-channel complex on embryonic chick motoneurons.

The actions of the putative quisqualate-selective agonist DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) were examined in identified embryonic chick motoneurons using gigaseal recording techniques and compared with properties of the selective non-NMDA excitatory amino acid agonists kainate and quisqualate. Pressure application of AMPA induces an inward going current when neurons are voltage-clamped at negative membrane potentials. The current-voltage relationship for this response is linear with reversal near 0 mV. Over the range of 1 microM-10 mM, the AMPA-induced current is dose-dependent with an ED50 of 40 microM. AMPA currents are insensitive to the selective NMDA receptor antagonist, 2-amino-5-phosphonovalerate, and the putative quisqualate selective blocker, glutamate diethyl ester, but are partially inhibited by kynurenic acid. In competition experiments, applications of saturating concentrations of AMPA and either kainate or quisqualate produce responses intermediate between the response to either agonist alone, indicating commonality in the mechanism of these agents. Applications of AMPA with the NMDA-selective agonist aspartate give an additive response. Analysis of current fluctuations indicates that AMPA, quisqualate, and kainate gate a channel with a primary conductance near 20 pS. Differences in maximal macroscopic current evoked by saturating concentrations of AMPA, kainate, and quisqualate cannot be explained by differences in mean channel open time as the most efficacious agonist, kainate, has the shortest channel open time (AMPA = 5.9 +/- 0.4 msec, kainate = 2.7 +/- 0.1 msec, quisqualate = 5.0 +/- 0.5 msec). Rather, kainate induces a greater frequency of channel opening. This finding contrasts with results obtained at the nicotinic ACh receptor, where the most efficacious agonists have the longest mean channel open time. Our results suggest that AMPA acts at the same receptor-channel complex as kainate and quisqualate on chick motoneurons and support the hypothesis that only 2 classes of excitatory amino acid receptor complexes exist in this preparation.

Amino Acids↗
PubMed1986

Brain monoamines and peptides: role in the control of eating behavior.

Studies of brain monoamines and neuropeptides have provided extensive evidence in support of their role in the control of normal eating behavior. In this process, the medial and lateral portions of the hypothalamus, working in conjunction with forebrain and hindbrain sites and with peripheral autonomic-endocrine systems, have a critical responsibility in balancing signals for hunger and satiety. Via its rich and biologically active neurotransmitter substances, the hypothalamus monitors and integrates the complex sensory and metabolic input concerning the nutritional status of the organism and transduces this information into appropriate quantitative and qualitative adjustments in food intake. The specific neurotransmitters for which there is the most extensive evidence for a physiological function include the eating-stimulatory substances norepinephrine (alpha 2), opioid peptides, pancreatic polypeptides, growth hormone-releasing factor, and gamma-aminobutyric acid; the eating-inhibitory substances dopamine, epinephrine, serotonin, cholecystokinin, neurotensin, calcitonin, glucagon, and corticotropin-releasing factor; and possibly other gut-brain peptides. From biochemical, pharmacological, and anatomical studies, hypotheses have been generated to explain the role of these various monoamines and neuropeptides in controlling total energy intake, in determining the amount and pattern of macronutrient selection, and in maintaining normal energy and nutrient stores under fluctuating conditions within the external environment.

Animals↗
PubMed1994

Natural course of Menière's disease in surgically-selected patients.

Menière's disease (MD) is considered a complex otologic disorder characterized by exacerbation and remission periods which often make its natural course unpredictable. Several studies in the past have analyzed the evolutionary course of MD through comparison between patients under medical treatment and those surgically treated. The present paper aimed to study the evolution of MD in a group of patients who were selected for endolymphatic sac surgery on the basis of a fluctuating stage and uncontrollable recurrent vertigo; some of them, however, did not undergo surgery for different reasons and were used as control for MD at a homogenous stage. Vertigo and tinnitus were improved by surgery in a significant number of patients in comparison with the non-surgical group. Hearing function, which improved few months after surgery in some patients, was found to deteriorate in the long run, in surgical and non-surgical groups. Sac surgery yielded significantly better results for two out of three Meniere's symptoms, i.e. vertigo and tinnitus, and can be considered to play a significant role in the therapy of MD at the fluctuating stage.

Ear, Inner↗
PubMed1994

[Direction of selection in experimental populations of Drosophila during cyclic change in their density].

The influence of cyclic fluctuations of Drosophila population density, which result from varying exploitation pressure and feeding conditions, on reorganization of the genotypic composition, evaluated for individual reproductive capacity, was studied. It was found that productivity, which was assessed in individual cultures by the number of adult offsprings, was higher for individuals that lived in low density conditions as compared to those in dense populations. These differences persisted in offsprings of compared individuals in two successive generations, thus testifying to their genetic determination. The genotypic composition of populations may change in one or two generations because of the selective pressure of density.

Animals↗