Anetoderma may reveal cutaneous plasmacytoma and benign cutaneous lymphoid hyperplasia.
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Adult↗
Biomedical subjects
P Andre
Publications and source records attributed to P Andre.
Influence of food on the disposition of the antidiabetic drug metformin in diabetic patients at steady-state.
The effect of food on the bioavailability of the antidiabetic drug metformin (Glucophage, Lipha Laboratories) was investigated in patients at steady-state. Seventeen diabetic patients (5 males and 12 females) treated with a long-term metformin therapy received their morning dose after an overnight fasting or after each of four types of breakfast: low protein, low fat, low carbohydrate or standard. Mean (+/- SD) and median areas under the serum concentration curves (AUC), maximum concentrations (Cmax) and time to reach the Cmax (Tmax) were calculated. Compared to fasting conditions, AUC and Cmax for metformin were bioequivalent after the four types of breakfast except the low fat (high carbohydrate) diet which had results slightly reduced (90% CI = [0.76-0.90]). The intraindividual variability was calculated and found to be lower than the interindividual variability.
Adult↗
The muscarinic agonist, bethanechol, enhances GABA-induced inhibition of Purkinje cells in the cerebellar cortex.
An important function of cholinergic projections to the cerebellar cortex may be to modulate the effects of classical afferent inputs to the cerebellar cortex. This hypothesis is supported by the recent observation that cholinergic agonists act at muscarinic receptors in the cerebellar cortex to facilitate Purkinje cell responses to glutamate, the excitatory neurotransmitter of parallel fibers [Brain Res., 617 (1993) 28-36]. Since Purkinje cell excitability is influenced by inhibitory input from basket and stellate cells as well as by excitatory input from granule cells and climbing fibers, the present study investigated whether muscarinic agonists could also modify the Purkinje cell responses to GABA, the putative inhibitory transmitter of basket and stellate neurons. In anesthetized rats, microiontophoretic application of bethanechol produced a long-lasting enhancement of GABA-evoked inhibition of firing of Purkinje cells in the cerebellar vermis (22/25 cells) regardless of whether bethanechol increased, decreased or failed to alter the basal firing rate of the cell. The muscarinic antagonist scopolamine prevented the bethanechol-induced increase in the GABA response. It appears, therefore, that cholinergic activation of muscarinic receptors enhances not only the excitatory but also the inhibitory component of cerebellar cortex circuitry. Further experiments are required to investigate whether this combination of effects may potentiate the signal processing capabilities of the cerebellar cortex.
Action Potentials↗
Noradrenergic agents in the cerebellar vermis affect adaptation of the vestibulospinal reflex gain.
In precollicular decerebrate cats, the vestibulospinal reflex (VSR) was intermittently recorded from the triceps brachii during sinusoidal roll tilt of the whole animal (at 0.15 Hz, +/- 10 degrees), leading to selective stimulation of labyrinth receptors. This reflex, tested during and after a 3-h period of sustained animal tilt at the same parameters indicated above, showed an adaptive increase in gain in some experiments but not in others. In a second group of experiments, however, rotation of the head (at 0.15 Hz, +/- 10 degrees) was associated with a synchronous body rotation (at 0.15 Hz, +/- 12.5 degrees) which led to an additional neck input, due to 2.5 degrees of out-phase body-to-head displacement. In these experiments, the VSR, tested every 10-15 min, consistently showed an adaptive increase in gain during and after a 3-h period of sustained vestibular and neck stimulation. Microinjection into the cerebellar anterior vermis of beta-adrenergic agents (0.25 microliters at 8 micrograms/microliters saline) produced slight and short-lasting changes in the basic amplitude of the VSR, due to the neuromodulatory influence of these agents on the Purkinje cells activity. In addition, the beta-adrenergic agonist isoproterenol brought to the light an adaptive process in those experiments in which no adaptation occurred during a sustained roll tilt of the whole animal. On the other hand, the beta-adrenergic antagonists propranolol or sotalol either suppressed the increase in gain of the VSR which occurred in other experiments during sustained animal rotation, or prevented the occurrence of an adaptive increase in gain during a continuous out-phase head and body rotation. We conclude that the adaptive changes in gain of the VSR are facilitated by the noradrenergic system acting within the cerebellar cortex through beta-adrenoceptors.
Adaptation, Physiological↗
Depression of the vestibulospinal reflex adaptation by intravermal microinjection of GABA-A and GABA-B agonists in the cat.
In decerebrate cats the gain of the vestibulospinal reflex (VSR), elicited by sinusoidal roll tilt of the animal at 0.15 Hz, +/- 10 degrees, was tested every 10-15 min during and after a sustained (3 h) period of roll tilt of the head at the parameters indicated above, associated with synchronous roll tilt of the body at 0.15 Hz, +/- 12.5 degrees; this stimulus led to 2.5 degrees of neck rotation, which was thus out of phase with respect to head rotation. In this condition the gain of the VSR progressively increased during the first h of neck-vestibular stimulation, to reach a plateau level at the end of the third h of stimulation. This adaptive process was followed for at least 1 h after stimulation. Microinjection into the zone B of the cerebellar anterior vermis of the GABA-A agonist muscimol (0.25 microliter at 8 micrograms/microliter saline) producing only a slight or negligible depression of the VSR gain in non-adaptive conditions, prevented the occurrence of the adapted increase in gain of the VSR following a 3-h period of sustained head and neck rotation. In addition, intravermal injection of the GABA-A or the GABA-B agonist muscimol or baclofen, respectively, at the same dose indicated above supressed the adapted increase in gain occurring after a 3-h period of continuous neck-vestibular stimulation. The effective sites were located into the zone B of the cerebellar anterior vermis, from which the direct corticocerebellar projection to the lateral vestibular nucleus originates. In conclusion, the results seem to indicate that the adaptive increase in gain of the VSR which occurs in decerebrate cats depend upon plastic changes which affect the Purkinje cells of the cerebellar anterior vermis. These changes were in fact suppressed by GABAergic inhibition of these neurons. The demonstration that the effects of the GABA agonists occurred suddenly makes unlikely the hypothesis that the cerebellar anterior vermis represents either a relay for adaptive changes occurring before it (for instance in the inferior olive) or else the generator of error signals that elicit plasticity in target structures (as in the vestibular nuclei).
Adaptation, Physiological↗
Injections of beta-noradrenergic substances in the cerebellar anterior vermis of cats affect adaptation of the vestibulospinal reflex gain.
In precollicular decerebrate cats, intermittent sinusoidal roll tilt of the whole animal (at 0.15 Hz, +/- 10 degrees) produced a vestibulospinal reflex (VSR), characterized by an increased EMG activity of the forelimb extensor triceps brachii during side-down and a decreased activity during side-up tilt. This reflex was first tested during and after a 3-h period of sustained animal tilt at the same parameters indicated above. An adaptive increase in gain of the VSR progressively developed in some experiments, but not in others. In a second group of experiments, however, sinusoidal roll tilt of the head (0.15 Hz, +/- 10 degrees) was associated with a synchronous roll tilt of the body (at 0.15 Hz, +/- 12.5 degrees). This additional stimulus led to 2.5 degrees of neck rotation, which was thus out of phase with respect to head rotation. In all these experiments, submitted to a 3-h period of sustained neck-vestibular stimulation, the gain of the VSR tested every 10-15 min consistently increased to reach the maximum at the end of the third hour of stimulation. This adaptive process was followed up to 1 h after stimulation. Microinjection into the hemivermal cortex of the cerebellar anterior lobe of the beta-noradrenergic antagonists propranolol or sotalol (0.25-0.50 microliter at 8 micrograms/microliter saline) produced only slight and short-lasting changes in the basic amplitude of the VSR, but always decreased or prevented the occurrence of the adaptive increase in gain of the VSR during sustained out of phase head-neck rotation. The same agents also suppressed the increase in gain of the VSR which occurred in some experiments during sustained roll tilt of the whole animal (at 0.15 Hz, +/- 10 degrees), leading to selective stimulation of labyrinth receptors. On the other hand, the beta-noradrenergic agonist isoproterenol (0.25 microliters at 8 micrograms/microliters saline) brought to the light the adaptive process in other experiments in which no adaptation occurred during sustained animal rotation. These effects occurred when the sites of injection were located within the zone B of the cerebellar anterior vermis, which projects to the lateral vestibular nucleus. In conclusion, the results indicate that the adaptive changes affecting the gain of the VSR in decerebrate cats are facilitated by the noradrenergic afferent system acting on the cerebellar vermis through beta-adrenoceptors.
Adaptation, Physiological↗
Activation of muscarinic receptors induces a long-lasting enhancement of Purkinje cell responses to glutamate.
The cerebellar cortex contains diffusely distributed cholinergic fibers and both muscarinic and nicotinic receptors. Behavioral studies suggest that an important function of this cholinergic innervation may be to modulate the effects of afferent input to the cerebellar cortex. The present study compared the effects of the muscarinic agonist bethanechol on basal firing rates and on glutamate-evoked firing of Purkinje cells in the vermis of the cerebellum of anesthetized rats. Microiontophoretic application of bethanechol produced a slowly developing, long-lasting enhancement of glutamate-evoked firing which was often disassociated from the bethanechol effect on the basal firing rate. Bethanechol increased the glutamate response of 22/33 Purkinje cells regardless of whether bethanechol increased, decreased or failed to alter the basal firing rate of the cell. The muscarinic antagonist scopolamine prevented the bethanechol-induced increase in the glutamate response. For 7/33 Purkinje cells, bethanechol decreased the glutamate-evoked response. However, this decrease did not appear to be mediated by muscarinic receptors because it was not blocked by scopolamine and it was mimicked by application of the vehicle alone. Acetylcholine application produced a long-lasting increase in the glutamate response of 4/5 Purkinje cells that was similar to the bethanechol effect. These data indicate that the cerebellar cholinergic system exerts a prominent modulatory influence on Purkinje cell excitability by acting through muscarinic receptors.
Acetylcholine↗
Adaptive modification of the cat's vestibulospinal reflex during sustained vestibular and neck stimulation.
In decerebrate cats, rotation about the longitudinal axis of the whole animal at 0.15 Hz, +/- 10 degrees produced an increased electromyogram (EMG) activity of the triceps brachii during side-down tilt and a decreased activity during side-up tilt. This vestibulospinal reflex (VSR) was tested before, during and after a sustained (3-h) period of roll tilt of the head at the parameters indicated above, associated with a synchronous roll tilt of the body at 0.15 Hz, but at the peak amplitude of either 12.5 degrees or 7.5 degrees. This additional stimulus led to 2.5 degrees of neck rotation, which was respectively out of phase (condition A) or in-phase (condition B) with head rotation. In a few instances the peak amplitude of neck rotation was increased to 5 degrees. In the first experimental condition A, the gain of the VSR (tested every 10-15 min) progressively increased, starting from the first hour of out of phase neck-vestibular stimulation to reach, on average, 241% of the control value at the end of the third hour of stimulation. On the other hand, in the second experimental condition B, the mean gain of the VSR first decreased to 82% during the first hour of in-phase neck-vestibular stimulation, but then increased to 165% of the corresponding control during the last hour of recording. In other experiments an adaptive increase in gain of the pure VSR occurred during a sustained (3-h) period of selective roll tilt of the whole animal, but it was less consistent and, on average, smaller in amplitude than that obtained during out of phase neck-vestibular stimulation. The adaptive changes in gain of the VSR described above were not associated with changes in the phase angle of the responses, and were also observed during the post-adaptation period. Further experiments indicated that the gain of the N-VSR, i.e. of the EMG responses to combined neck-vestibular stimulation, displayed a prominent adaptive increase during the sustained out of phase stimulation, but not during the in phase stimulation.
Adaptation, Physiological↗
Extravasation of salivary secretions and mumps infection of the submandibular gland.
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Adult↗
Nicotinic receptors in the cerebellar vermis modulate the gain of the vestibulospinal reflexes in decerebrate cats.
1. The possibility that the cholinergic afferent system terminating in the vermal cortex of the cerebellar anterior lobe acts on the target neurons by utilizing nicotinic receptors has been investigated in decerebrate cats by testing the effects of local microinjection of cholinergic nicotinic agonists and antagonists on posture as well as on the dynamic characteristics of the vestibulospinal (VS) reflexes. 2. Unilateral injection into the vermal cortex of the culmen of nicotine (0.25 microliter at the concentration of 0.05-0.5 microgram/microliter saline) decreased the extensor tonus in the ipsilateral forelimb, while the extensor tonus in the contralateral forelimb increased. The some agent significantly increased the gain of the first harmonic component of the EMG responses of the ipsilateral and more prominently also of the contralateral triceps brachii to animal tilt. However, the phase angle of the responses remained bilaterally unmodified. The effects described above were first observed 5-10 min after the injection, reached the peak after 40-60 min and persisted for at least 2-3 h before disappearing. 3. The effective area was located between the second and the fourth folium of the cerebellar vermis rostral to the fissura prima, at the laterality of 1.4-1.8 mm. This area, which upon cathodal stimulation suppressed the spontaneous EMG activity of the ipsilateral triceps brachii, actually corresponds to the zone B of the cerebellar cortex which exerts a direct inhibitory influence on the lateral vestibular nucleus. Moreover, the effects were dose-dependent. 4. Microinjection of nicotinic antagonists of both the ganglionic type (hexamethonium, 0.25 microliter at 4 micrograms/microliters saline) and the neuromuscular type (d-tubocurarine, 0.25 microliter at 7 micrograms/microliters saline) produced a postural asymmetry opposite in sign to that elicited by nicotine. The same agents also decreased the response gain of the triceps brachii of both sides to animal tilt recorded either under normal conditions or after previous injections of nicotine. 5. The experiments indicate that the cholinergic system is involved in the control of posture as well as in the gain regulation of the VS reflexes. Previous histochemical studies had shown that the cholinergic fibers terminate not only on Purkinje (P)-cells, but also and more prominently as mossy fibers ending on granular cells. This system may thus affect the discharge of P-cells and related inhibitory interneurons not only ipsilaterally but also contralaterally to the side of the injection.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Increased acetylcholine and quisqualate responsiveness after blockade of GABAB receptors.
The aim of this study was to gain further insight into the function of cortical GABAB receptors. In chloral hydrate-anaesthetized rats, microiontophoretic administration of the GABAB receptor blocker CGP 35348 induced a moderate increase in firing of spontaneously active neurons in the rostral and caudal sensorimotor cortex. This increase in cell firing was accompanied by a reduction in the baclofen-induced inhibition of cell activity. In contrast to the GABAA receptor antagonist bicuculline methiodide, CGP 35348 did not induce any paroxysmal discharges. The excitatory responses of rostral cortical neurons elicited by iontophoretically applied acetylcholine and quisqualate were potentiated in most neurons after both microiontophoretic and intravenous administration of CGP 35348. The potentiation was observed in the absence of any change in the spontaneous firing rate. These effects were dose-dependent for both routes of administration. The potentiation of the quisqualate response was reversed by intravenously applied baclofen. In conclusion, these findings suggest that cortical GABAB receptors are involved in the control of cortical neuronal excitability.
Acetylcholine↗
Microinjections of vasopressin in the locus coeruleus complex affect posture and vestibulospinal reflexes in decerebrate cats.
Vasopressin (VP) acts as a neurotransmitter or a neuromodulator on noradrenergic locus coeruleus (LC) neurons by exciting them. Experiments were performed in precollicular decerebrate cats to investigate whether direct infusion of VP into the LC complex of one side produced changes in posture as well as in the gain of vestibulospinal reflexes acting on forelimb extensors. Unilateral microinjection of 0.25 microliters VP solution (10(-11) micrograms/microliters saline) into the LC complex increased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either remained unmodified or slightly decreased. The amplitude of modulation and thus the response gain of both the ipsilateral and the contralateral triceps brachii to roll tilt of the animal leading to stimulation of labyrinth receptors decreased (t-test, P less than 0.001 for both the ipsilateral and the contralateral responses). Moreover, a slight decrease in phase lead of the responses was observed. These findings occurred 5-10 min after the injection, were fully developed within 30 min and disappeared in about 2 h. The changes in posture as well as in the gain of vestibulospinal reflexes described above were site specific and depended upon the injected neuropeptide. They were attributed to tonic activation of presumptive noradrenergic neurons, which exert a facilitatory influence on limb extensor motoneurons either directly, by utilizing the coeruleospinal pathway, or indirectly by inhibiting the dorsal pontine reticular formation and the related medullary inhibitory reticulospinal neurons.
Animals↗
Interferon production in severe hemophiliacs with and without HIV antibodies.
The interferon (IFN) system, both serum IFN levels and the in vitro IFN production, was investigated in 38 clinically asymptomatic multitransfused hemophiliacs, half positive and half negative for HIV antibodies. In most patients, no circulating IFN was detected; similar levels of IFN-alpha were obtained after peripheral blood mononuclear cell (PBMC) stimulation with Sendai virus both in hemophiliacs and controls, while production of IFN-gamma following stimulation with phytohemagglutin (PHA) was diminished in a large number of patients irrespective of their HIV serology. These data indicate that the deficiency in IFN-gamma generation is not only related to HIV contamination but may be a direct consequence of the chronic antigenic stimulation through Factor VIII concentrates.
HIV Seropositivity↗
Muscarinic receptors in the cerebellar vermis modulate the gain of the vestibulospinal reflexes in decerebrate cats.
1. The Purkinje (P)-cells of the cerebellar vermis, which exert a prominent influence on posture as well as on the gain of vestibulospinal (VS) reflexes, are under the control not only of the classic mossy fibers and climbing fibers which liberate excitatory amino acids as neurotransmitter, but also of cholinergic afferents. The role of these afferents was investigated in precollicular decerebrate cats by using the method of local microinjection of cholinergic agents into appropriate areas of the cerebellar cortex. 2. Unilateral injection into the vermal cortex of the culmen of the non-selective cholinergic agonist carbachol (0.25 microliters at 0.5 micrograms/microliters saline) produced a postural asymmetry, characterized by a slight decrease of the extensor tonus in the ipsilateral forelimb and an increased tonus in the contralateral forelimb. Moreover, the gain of the EMG responses of the ipsilateral and the contralateral triceps brachii to animal tilt increased significantly, while no significant changes in the phase angle of the responses were observed. These effects started 5-10 min after the injection and persisted for at least 2 hours before disappearing. Similar but smaller effects were obtained after injection of eserine, an inhibitor of acetylcholinesterase. Thus, the effects could be produced by increasing the naturally present amount of acetylcholine (ACh). 3. The changes in posture and gain of the VS reflexes described above utilized in part at least muscarinic receptors, since effects similar to those induced by carbachol injection were also obtained after unilateral microinjection into the vermal cortex of the culmen of the muscarinic agonist bethanechol (0.25 microliters at 0.1 micrograms/microliters). On the other hand opposite effects, characterized by an increased postural activity in the ipsilateral forelimb associated with a decreased activity in the contralateral forelimb, as well as by a reduced gain of the EMG responses of the triceps brachii of both sides to animal tilt were observed in other experiments after local microinjection of the muscarinic antagonist scopolamine (0.25 microliter at 4-8 micrograms/microliters saline). Evidence for muscarinic supersensitivity was obtained following repetitive injections of scopolamine into the cerebellar vermis. 4. The area which upon injection of the cholinergic agents modified the postural activity as well as the gain of the VS reflexes was located within the third and/or the fourth folium rostral to the fissura prima (culmen), at the laterality of 1.4-1.8 mm with respect to the midline.(ABSTRACT TRUNCATED AT 400 WORDS)
Afferent Pathways↗
Effects of microinjection of vasopressin in dorsal pontine reticular structures on the gain of vestibulospinal reflexes in decerebrate cats.
1. The possibility that vasopressin (VP) acts on the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system to control posture as well as the vestibulospinal reflexes has been investigated by injecting small doses of VP in precollicular decerebrate cats. 2. Unilateral microinjection of VP (0.25 microliters at the concentration of 10(-11) micrograms/microliters saline) in the pRF decreased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either decreased or increased. The same injection also produced a moderate or a prominent increase in gain of the multiunit EMG responses of the ipsilateral triceps brachii to roll tilt of the animal (t-test, P less than 0.001 for either group of responses). In the first instance the response gain of the contralateral triceps brachii to animal tilt slightly increased, while the pattern of response remained always of the alpha-type, as shown for the ipsilateral responses (increased EMG activity during ipsilateral tilt and decreased activity during contralateral tilt). In the second instance, however, the response gain showed only slight changes, while the pattern of responses reversed from the alpha- to the beta-type. These findings occurred 5-20 min after the injection, fully developed within 30-60 min and disappeared in about 2-3 hours. 3. The structures responsible for the postural and reflex changes described above were located in the dorsal pontine tegmental region immediately ventral to the LC, and included the peri-LC alpha and the surrounding dorsal pRF. The induced effects depended upon the injected neuropeptide, since previous injection of an equal volume of saline stained by the pontamine sky blue dye into the same dorsal pontine area was ineffective. 4. We postulated that VP exerts an excitatory influence on ipsilateral dorsal pRF neurons. The increased discharge of these neurons and the related medullary inhibitory RS neurons would lead to a decreased postural activity in the ipsilateral limbs. However, since these inhibitory RS neurons fire out of phase with respect to the excitatory vestibulospinal neurons, it appears that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition that affects the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Endothelial and smooth muscle cells from the same rat aorta.
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Animals↗
In vitro culture and cloning of Toxoplasma gondii in a newly established cell line derived from TG180.
A new non-adherent cell line derived from spontaneous mutation of TG180 cells was adapted to in vitro culture in a defined culture medium. This cell line can be used for in vitro production and cloning of Toxoplasma gondii by limiting dilution.
Animals↗
Biochemical and functional association between CD8 and H-2 at the surface of a T cell clone.
In an attempt to define structures interacting with CD8 molecules during activation of CD8+ cells, immunoprecipitates of CD8 and Tcr-CD3 molecules from lysates of a surface-labeled CTL clone were analyzed. No proteins other than the known Tcr alpha/beta and associated CD3 components were detected in either anti-Tcr or anti-CD3 immunoprecipitates, whether or not the CTL clone had been activated. However, anti-CD8 antibodies co-precipitated class I MHC heavy chain and associated beta 2-microglobulin in all conditions. The latter co-precipitation was shown to result from "cis-type" interactions between CD8 and class I MHC proteins on the same cell and to involve a degree of selectivity, as class I MHC molecules were absent from immunoprecipitates of highly expressed cell surface molecules such as LFA-1. A further analysis of cell surface molecular distribution during antigen-dependent CTL-target cell interaction by double fluorescence-microscopy in non-activating conditions indicated that an increased density of CTL class I molecules was found in the CTL-target cell contact zone of most conjugates with redistributed CD8 molecules. A possible role for "cis-type" class I MHC-CD8 interactions in the dynamics of CTL-target cell contacts is proposed.
Animals↗