Biomedical subjects

P Andre

Publications and source records attributed to P Andre.

At least 37 records · Page 2Linked to original sources

PubMed1998

Effect of siderophores, catecholamines, and catechol compounds on Listeria spp. Growth in iron-complexed medium.

Almost all bacteria require iron for growth and virulence expression. However, Listeria spp. do not produce any siderophore for iron acquisition. Representative strains of each of the six species of Listeria were examined for their ability to use various compounds as iron suppliers in iron-restricted medium. Here we show that L. monocytogenes, L. innocua, L. ivanovii, L. welshimeri, L. seeligeri, and L. grayi were able to use exogenous siderophores and various catechol ligands, including catecholamines, to overcome growth inhibition induced by tropolone, an iron chelating agent. In contrast, no growth promoting effect was observed with normetanephrine or 4-hydroxy-3-methoxyphenylglycol-piperazine salt, which indicates that the o-diphenol function of the ligand must be free to allow iron acquisition. Furthermore, we demonstrate that catecholamines do not act through specific bacterial receptors, because no difference in growth stimulation was observed between [+]- and [-]-norepinephrine. These results show that utilization of a variety of catechol compounds to acquire iron is a general phenomenon in the genus Listeria.

Catecholamines↗

PubMed1998

Amino-acid change in the Epstein-Barr-virus ZEBRA protein in undifferentiated nasopharyngeal carcinomas from Europe and North Africa.

Different Epstein-Barr-virus(EBV) variants were found to be associated with nasopharyngeal carcinoma (NPC). The type-C variant lacks the BamHI site between the BamHI W1* and I* regions and the type-f variant has an extra BamHI site in the BamHI F fragment. The BNLF1 gene (which encodes the LMP1 protein) from a nude-mouse-passaged CAO strain and from NPC biopsies from Taiwanese patients also exhibits variations resulting in structural and functional differences in the protein. The BZLF1 gene encodes the ZEBRA protein which triggers the EBV lytic cycle. A difference has been observed in 8 amino acids in the ZEBRA sequence in B95-8 (Z95) and P3HR1 (ZP3) cell lines. EBV found in NPC biopsies and peripheral-blood cells from Asians was predominantly of the ZP3 type (72%), while 81% of samples from different EBV-associated diseases and peripheral-blood cells from North Africa or Europe were of the Z95 type. We found that an alanine 206 had been replaced by a serine in the Z95 sequence in 72% of the NPC biopsies from European and North African patients. The Zser206 variant is found in a significantly lower percentage (p < 0.001) of other EBV-positive tissues from individuals in the same region (10-33%). In contrast, a 30-bp deletion is observed near the 3' end of the LMP1 gene in the majority of EBV (86%) from NPC and peripheral-blood cells from Asians, whereas a significantly lower percentage (p < 0.001) of NPC biopsies from European and North African patients (56%) have this deletion, as do lymphocytes from control individuals from the same region (36 and 55% respectively).

Africa, Northern↗

PubMed1998

Convergence of directional vestibular and neck signals on cerebellar purkinje cells.

Convergence of spatially oriented vestibular and neck signals within the cerebellar anterior vermis in decerebrate cats was studied by recording the simple spike discharge of Purkinje (P) cells during wobble either of the whole animal (vestibular input) or of the body under a fixed head (neck input) at 0.156 Hz, 5 degrees and 2.5 degrees , respectively. Both clockwise (CW) and counterclockwise (CCW) rotations were performed. Units that had equal response amplitudes to CW and CCW rotations (narrowly tuned neurons) were described by a single vector (Smax), characterized by a gain, a direction and a temporal phase. Units with different response amplitudes to CW and CCW rotation (broadly tuned neurons) were described by two vectors (Smax and Smin). In addition to these bidirectional units, there were also unidirectional units which responded either to CW or CCW rotation; in these cases the gain of Smax equals that of Smin. On the whole, 77% and 63% of the P cells responding to vestibular and neck stimulation, respectively, showed a bidirectional broadly tuned or unidirectional behavior. These response patterns were attributed to the convergence of signals with different spatial and temporal properties. About 50% of the P cells from which recordings were made responded to stimulation of both sensory systems. However, the gains of the Smax vectors of the neck responses were much greater than those of the vestibular responses, at least for small amplitudes of rotation, and were positively correlated with them. Usually the differences in the orientation components of the neck and vestibular Smax vectors were larger, while the differences in temporal phases were smaller than 90 degrees . These findings suggest that periodic changes in the phase difference and gain ratio of the neck to the vestibular response may occur during dynamic displacement of the head over the body, depending on the stimulus direction. As a result of these data, the P cells of the cerebellar vermis are expected to show prominent responses to head rotation, which could affect the spatially organized postural responses by utilizing vestibular and reticular targets.

Animals↗

PubMed1998

Spatiotemporal response properties of cerebellar Purkinje cells to neck displacement.

The activity of 184 Purkinje cells and 58 unidentified neurons located within the cerebellar anterior vermis was recorded in decerebrate cats during wobble of the body under a fixed head. This stimulus induced a neck displacement of constant amplitude (2.5 degrees) whose direction rotated at the constant velocity of 56.2 degrees/s on the horizontal plane, both in the clockwise and counterclockwise directions. It was then possible to evaluate the spatiotemporal characteristics of unit responses to neck displacement in the vertical planes; 131 of 184 Purkinje cells (71%) and 35 of 58 unidentified cells (60%) responded to clockwise and/or counterclockwise rotations. In particular, among the responsive units, 44% of the Purkinje cells and 37% of the unidentified cells showed an equal amplitude modulation during clockwise and counterclockwise rotations. These units are expected to show a maximal response sensitivity for neck displacement in a preferred direction, a null response for perpendicularly oriented stimuli and a constant temporal phase (narrowly tuned neurons). In 28% of the Purkinje cells and 40% of the unidentified cells, responses of different amplitudes were observed during clockwise and counterclockwise rotations. These neurons should display a preferred direction of response to neck displacement, lack of null response directions and a temporal phase changing with the stimulus direction (broadly tuned neurons). Finally, 27% of the Purkinje cells and 23% of the unidentified cells responded only to wobble in the clockwise or counterclockwise direction (unidirectional units). This behavior predicts equal sensitivities for all the directions of neck displacement and a response phase changing linearly with the direction of neck displacement. A maximal sensitivity vector (Smax), aligned with the preferred direction of the neuron, was evaluated for the bidirectional narrowly tuned and broadly tuned units. Its amplitude and temporal phase corresponded to the response characteristics expected for stimuli in the preferred direction of the cell. Smax directions were distributed over the horizontal plane. Most of them, however, were closer to the pitch than to the roll axis and pointed towards the animal's tail. Among pitch-related Purkinje cells, the temporal phase of Smax was small with a predominance of phase lags; phase leads of rather large amplitude were usually observed for roll-related Purkinje cells. The possibility that the recorded population of units coded the direction of neck displacement was tested by assuming that each cell gave a vectorial contribution related to its response properties and that the vectorial sum of such contributions represented the outcome of the population code. Dynamic body-to-head displacements in four different directions were simulated and for each direction 12 population vectors were evaluated at regular intervals of the stimulus cycle. The direction of the population vector was related to that of the stimulus, but the correspondence was close only for the pitch direction. Moreover, the amplitude of the population vector depended upon the direction of the stimulus, being larger for pitch than for roll displacements. Due to the efferent connections of the explored cerebellar region, the neuronal signals generated by the Purkinje cell population are probably transferred to the spinal cord, where they may differentially affect the amplitude and the spatial properties of the neck reflexes according to the direction of neck displacement.

Animals↗

PubMed1997

Selectivity of the major histocompatibility complex class II presentation pathway of cortical thymic epithelial cell lines.

Major histocompatibility complex (MHC) restriction of the immune response is established during positive selection of T cells in the thymus. This occurs mainly through interactions of T cell receptor of developing thymocytes with MHC/peptide ligands on cortical thymic epithelial cells (TEC). An ongoing controversy concerns the origin and the role of peptides involved in the positive selection of thymocytes. Evidence provided here shows that processing of MHC class II complexes in cortical TEC differs from that of medullary TEC. Removal of the invariant chain associated with MHC class II complexes was rapid and complete in medullary TEC which present peptides from both exogenous and cytosolic origin. In cortical TEC, a large fraction of class II dimers remained associated with a 10-12-kDa fragment of invariant chain (Ii). Incomplete removal of Ii correlated with the inability of cortical TEC to present peptides from exogenous origin. However, presentation of peptides from cytosolic proteins by cortical TEC remained possible. Thus, most peptides from exogenous proteins may be excluded from participating in positive selection of CD4+ T cells by a mechanism limiting Ii breakdown.

Animals↗

PubMed1997

Spatiotemporal response properties of cerebellar Purkinje cells to animal displacement: a population analysis.

The hypothesis that corticocerebellar units projecting to vestibulospinal neurons contribute to the spatiotemporal response characteristics of forelimb extensors to animal displacement was tested in decerebrate cats in which the activity of Purkinje cells and unidentified cells located in the cerebellar anterior vermis was recorded during wobble of the whole animal. This stimulus imposed to the animal a tilt of fixed amplitude (5 degrees) with a direction moving at a constant angular velocity (56.2 degrees/s), both in the clockwise and counterclockwise directions over the horizontal plane. Eighty-three percent (143/173) of Purkinje cells and 81% (42/52) of unidentified cells responded to clockwise and/or counterclockwise rotations. In particular, 116/143 Purkinje cells (81%) and 32/42 unidentified cells (76%) responded to both clockwise and counterclockwise rotations (bidirectional units), while 27/143 Purkinje cells (19%) and 10/42 unidentified cells (24%) responded to wobble in one direction only (unidirectional units). For the bidirectional units, the direction of maximum sensitivity to tilt (Smax) was identified. Among these units, 24% of the Purkinje cells and 26% of the unidentified cells displayed an equal amplitude of modulation during clockwise and counterclockwise rotations, indicating a cosine-tuned behavior. For this unit type, the temporal phase of the response to a given direction of tilt should remain constant, while the sensitivity would be maximal along the Smax direction, declining with the cosine of the angle between Smax and the tilt direction. The remaining bidirectional units, i.e. 57% of the Purkinje cells and 50% of the unidentified cells displayed unequal amplitudes of modulation during clockwise and counterclockwise rotations. For these neurons, a non-zero sensitivity along the null direction is expected, with a response phase varying as a function of stimulus direction. As to the unidirectional units, their responses to wobble in one direction predict equal sensitivities along any tilt direction in the horizontal plane and a response phase that changes linearly with the stimulus direction. By comparing these data with those obtained previously during selective stimulation of macular receptors by a 5 degrees off-vertical axis rotation, it appeared that the directions of maximum sensitivity to tilt were distributed over the whole horizontal plane of stimulation, in both conditions. However, co-stimulation of macular and canal receptors during wobble decreased the proportion of unidirectional units, while that of the bidirectional, namely broadly tuned units, increased. In addition, while the average gain of the Smax vector of the bidirectional units was comparable, the temporal phase of this vector tended to show a more prominent phase leading behavior during wobble with respect to off-vertical axis rotation. The possibility that the tested neurons formed a population which coded the direction of head tilt in space was also investigated using a modified version of the classical population vector analysis. It was shown that for each selected time in the tilt cycle the direction of the population vector closely corresponded to that of the head tilt, while its amplitude was related to that of the stimulus. We conclude that the broad distribution of the response vector orientation of units located in the cerebellar anterior vermis represents an appropriate substrate for the cerebellar control of vestibulospinal reflexes involving extensor muscles during a variety of head tilts. In view of their efferent projections to the vestibular and fastigial nuclei, the cerebellar anterior vermis may provide a framework for the spatial coding of vestibular inputs, giving equal emphasis to both side-to-side and fore-aft stability.

Animals↗

PubMed1997

Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes.

Listeria monocytogenes is a ubiquitous potentially pathogenic organism requiring iron for growth and virulence. Although it does not produce siderophores, L. monocytogenes is able to obtain iron by using either exogenous siderophores produced by various microorganisms or natural catechol compounds widespread in the environment. In the presence of tropolone, an iron-chelating agent, growth of L. monocytogenes is completely inhibited. However, the growth inhibition can be relieved by the addition of dopamine or norepinephrine under their different isomeric forms, while the catecholamine derivatives 4-hydroxy-3-methoxyphenylglycol and normetanephrine did not relieve the inhibitory effect of tropolone. Preincubation of L. monocytogenes with chlorpromazine and yohimbine did not antagonize the growth-promoting effect of catecholamines in iron-complexed medium. In addition, norepinephrine stimulated the growth-promoting effect induced by human transferrin in iron-limited medium. Furthermore, dopamine and norepinephrine allowed 55Fe uptake by iron-deprived bacterial cells. The uptake of iron was energy dependent, as indicated by inhibition of 55Fe uptake at 0 degrees C as well as by preincubating the bacteria with KCN. Inhibition of 55Fe uptake by L. monocytogenes was also observed in the presence of Pt(II). Moreover, when assessed by a whole-cell ferric reductase assay, reductase activity of L. monocytogenes was inhibited by Pt(II). These data demonstrate that dopamine and norepinephrine can function as siderophore-like compounds in L. monocytogenes owing to their ortho-diphenol function and that catecholamine-mediated iron acquisition does not involve specific catecholamine receptors but acts through a cell-bound ferrireductase activity.

Catecholamines↗

PubMed1996

Which experimental model to choose to study arterial thrombosis and evaluate potentially useful therapeutics?

The use of experimental models of arterial thrombosis both in vivo and ex vivo in animals and ex vivo in humans is an obligatory step for the understanding of mechanisms involved in thrombogenesis as well as in the evaluation of anti-thrombotic therapeutics. Arterial thrombogenesis is a complex phenomenon which involves multiple systems, mechanisms and parameters. Therefore studies of thrombogenesis from a pathological as well as a therapeutic point are necessary for understanding this problem in its entirety. For these reasons, it is necessary to use models as representative as possible of the human pathological condition. Besides these theoretical requirements, practical needs have also to be fulfilled (accessibility of the models, adaptation to the type of the technique to different animal model and/or of the size of the animal to the amount of molecule available, cost...) which necessarily lead to some compromises. In this review we have tried to underline the criteria for the choice, characteristics, advantages and disadvantages of the major models commonly accepted and used, in such a form that the reader who may not be an expert in the field would be led either to a choice of a particular model for a specific purpose or to appreciate a paper or a report based on an experimental model of arterial thrombosis. In vitro models of arterial thrombosis are so far removed from reality and due to their nature can generate so much artifacts that we have omitted their discussion from this paper.

Animals↗

PubMed1995

Responses of Purkinje cells in the cerebellar anterior vermis to off-vertical axis rotation.

Responses of 67 Purkinje cells (P-cells) and 44 unidentified neurons (U-cells) located in the cerebellar anterior vermis were recorded in decerebrate cats during off-vertical axis rotation (OVAR). This stimulus consisted of a slow constant velocity (9.4%/s) rotation in the clockwise (CW) and counterclockwise (CCW) directions around an axis inclined by 5 degrees with respect to the vertical. OVAR imposes on the animal head a 5 degrees tilt, whose direction changes continuously over the horizontal plane, thus eliciting a selective stimulation of macular receptors. A total of 27/67 P-cells (40%) and 24/44 U-cells (55%) responded to both CW and CCW rotations. For these bidirectional units, the direction of maximum sensitivity to tilt (Smax) could be identified. Smax directions were distributed over the whole horizontal plane of stimulation. Among bidirectional neurons, 48% of the P-cells and 33% of the U-cells displayed an equal amplitude of modulation during CW and CCW rotations, indicating a cosine-tuned behaviour. In these instances, the temporal phase of the unit response to a given direction of tilt remained constant, while the sensitivity was maximal along the Smax direction and declined with the cosine of the angle between Smax and the tilt direction. The remaining bidirectional units displayed unequal amplitudes of modulation during CW and CCW rotations. For these neurons, a nonzero sensitivity along the null direction was expected and the response phase varied as a function of stimulus direction. Finally, 31% and 23% of P-cells and U-cells, respectively, responded during OVAR in one direction only (unidirectional units). This behaviour predicts equal sensitivities along any tilt direction in the horizontal plane and a response phase that changes linearly with the stimulus direction. The posibility that the tested neurons formed a population which coded the direction of head tilt in space was also investigated. The data from the whole population of cells were analysed using a modified version of vectorial analysis. This model assumes that for a particular tilt each cell makes vectorial contributions; the vectorial sum of these contributions represent the outcome of the population code and points in the direction of head tilt in space. Thus, a dynamic head tilt along four representative directions was simulated. For each of the four directions, 12 population vectors were calculated at regular time intervals so as to cover an entire cycle of head tilt. The results indicate that for each selected time in the cycle the direction of the population vector closely corresponded to that of the head tilt, while its amplitude was related to the amount of head tilt. These data were particularly obtained for the P-cells. In view of their efferent connections, the cerebellar anterior vermis may provide a framework for the spatial organization of vestibulospinal reflexes induced by stimulation of otolith receptors.

Animals↗

PubMed1995

Calibration of an in vitro assay system using a non-adherent cell line to evaluate the effect of a drug on Toxoplasma gondii.

A TG 180 non-adherent cell culture with Toxoplasma gondii and spiramycin was performed in order to calibrate TG 180 cells used in a therapeutic assay system. TG 180 cells were infected with the RH strain of T. gondii, and spiramycin was added at final concentrations of 1, 2, 4, 8, 12, 16, 20 and 25 micrograms/ml. A least-squares linear regression with confidence interval was calculated from the experimental curve and allowed the determination of the 50% inhibitory concentration of spiramycin. The IC50 of 13.7 micrograms/ml obtained is comparable with the results of the literature. The system including TG 180 cells (recently cultured in vitro) provides a rapid, accurate and economical determination of the effects of a drug on Toxoplasma gondii.

Animals↗

PubMed1995

Utilization of exogenous siderophores and natural catechols by Listeria monocytogenes.

Listeria monocytogenes does not produce siderophores for iron acquisition. We demonstrate that a number of microbial siderophores and natural iron-binding compounds are able to promote the growth of iron-starved L. monocytogenes. We suggest that the ability of L. monocytogenes to use a variety of exogenous siderophores and natural catechols accounts for its ubiquitous character.

Animals↗

PubMed1995

Characterization of five esterases from Listeria monocytogenes and use of their electrophoretic polymorphism for strain typing.

Esterases from Listeria monocytogenes strains isolated from cheeses were analyzed by starch gel electrophoresis. Five esterases, numbered from EST 1 to EST 5 in order of decreasing anodal migration, were identified. The EST 1, EST 3, EST 4, and EST 5 set was most active toward alpha-naphthyl propionate, while EST 2 was most active toward alpha-naphthyl acetate. Results from inhibitor studies suggest that all of these esterases were EC class 3.1.1.1 carboxylesterases, except that EST 1 and EST 3 also showed some sensitivity to parahydroxymercuribenzoate. Polymorphism of these five esterases was observed in the population. Twelve esterase patterns were defined and used to subdivide serotypes.

Bacterial Typing Techniques↗

PubMed1995

The effects of metformin on the capillary permeability to albumin in women patients with cyclic edema.

An experimental work has suggested the efficacy of metformin, an oral antidiabetic agent, on capillary permeability. This agent has been tested in 10 women patients with cyclic edema, 7 of them being obese. The capillary permeability to albumin studied by an isotope test derived from Landis's method was initially increased. After a mean of six-weeks of treatment the albumin retention and an index demonstrating the interstitial protein elimination through the lymph route were significantly improved. Concomitantly, the swelling feelings were reduced in 8 cases and the lower limb edema had decreased or disappeared in 8 of 9 patients who initially presented these symptoms. The effects of metformin are beneficial and have been observed to be independent of glycemic change. The results suggest a special effect of this agent on the microcirculation. Nevertheless, a controlled study is required.

Adult↗

PubMed1995

Role of the spinocerebellum in adaptive gain control of cat's vestibulospinal reflex.

In decerebrate cats, a 3-h period of sustained roll tilt of the head (at 0.15 Hz. +/- 10) leading to selective stimulation of labyrinth receptors, associated with a synchronous roll tilt of the body (at 0.15 Hz., +/- 12.5) leading to 2.5 degrees out-of-phase neck rotation produced an adaptive increase in gain of the vestibulospinal reflex (VSR) elicited by roll tilt of the animal at 0.15 Hz, +/- 10 degrees. This increase reached the maximum at the end of the third h of stimulation and persisted unmodified during the first h after stimulation. Microinjection into zone B of the cerebellar anterior vermis of the GABA-A agonist muscimol (0.25 microliter at 8 micrograms/microliters saline), producing only a slight or negligible depression of the VRS 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-body rotation. Moreover, intravermal injection of the GABA-A agonist muscimol or the GABA-B agonist baclofen (0.25 microliter at 8 or 2 micrograms/microliters saline, respectively) suppressed the already adapted VSR gain. It is postulated that the adaptive increase in gain of the VSR following a sustained neck-vestibular stimulation depends on plastic changes which affect the Purkinje cells of the cerebellar anterior vermis.

Animals↗

PubMed1995

Role of muscarinic receptors in the cerebellar control of the vestibulospinal reflex gain: cellular mechanisms.

Most of the inhibitory Purkinje (P-) cells of the cerebellar anterior vermis fire out-of-phase with respect to the excitatory vestibulospinal neurons during roll tilt of the animal, thus exerting a positive influence on the gain of the vestibulospinal reflex (VSR). The responses of these P-cells depend on activation of glutamatergic excitatory mossy fibers-granule cells, but they are likely to be shaped by GABAergic inhibitory interneurons. The cerebellar cortex contains cholinergic fibers and both muscarinic and nicotinic receptors. In decerebrate cats intravermal injection of the muscarinic agonist bethanechol increased the VSR gain. The cellular mechanisms underlying these gain changes were studied in anesthetized Sprague-Dawley rats by microiontophoresis. Application of bethanechol (10-60 nA, 300 s) increased the response of vermal P-cells to pulses of glutamate (22/33 cells) or GABA (23/25 cells). These effects, which were blocked by the muscarinic antagonist scopolamine, lasted up to 15-40 min and occurred regardless of whether bethanecol altered the basal firing rate of the cells. We propose that the increase of P-cell responses to both excitatory and inhibitory neurotransmitters following activation of muscarinic receptors enhances the amplitude of modulation of these neurons to animal tilt, thus increasing the gain of the VSR.

Animals↗

PubMed1995

Modulation of vestibulospinal reflexes through microinjection of GABAergic agents in the dorsal pontine tegmentum of decerebrate cats.

1. The locus coeruleus (LC) neurons control posture as well as the gain of the vestibulospinal (VS) reflexes either through direct coeruleospinal (CS) projections or by inhibiting the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) systems. After the demonstration that the LC neurons are under the inhibitory control of GABAergic afferents, experiments were performed to investigate whether the same system could also suppress the activity of the dorsal pRF, thus intervening in the control of posture and VS reflexes. 2. In precollicular decerebrate cats, unilateral microinjection into the dorsal pRF of the GABA-A antagonist bicuculline or the GABA-B antagonist faclofen (0.13-0.25 microliter at 2.5 micrograms/microliter saline) decreased the tonic contraction of the ipsilateral triceps brachii, but greatly increased the amplitude of the EMG responses of the same muscle to roll tilt of the animal (at 0.15 Hz, +/- 10 degrees). This increase in gain of the VS reflexes was not associated with great changes in phase angle of the responses, which were always characterized by an increased EMG activity during ipsilateral tilt and a decreased activity during contralateral tilt. The same injection also produced in some instances a slight decrease of the extensor tonus of the contralateral forelimb, associated with a moderate increase in the amplitude of modulation and thus in the response gain of contralateral triceps brachii to labyrinth stimulation. However, when the ipsilateral effects were prominent, the response gain of the contralateral triceps muscle was slightly depressed, while the pattern of response reversed. 3. The changes in posture and reflexes described above appeared 5-10 min after unilateral injection of the GABA antagonists in the pRF, reached the highest values in about 30 min and fully recovered to the control levels within 2 h after the injection. These effects were not due to irritative phenomena following injection of the fluid, since neither changes in posture nor in the response gain of the triceps brachii to labyrinth stimulation were observed after injection of an equal volume of vehicle in the pRF of that side. On the other hand, an increase in postural activity associated with a decrease in the response gain of the ipsilateral and contralateral triceps brachii to animal tilt was observed after unilateral microinjection into the dorsal pRF of GABA agonists. 4. Histological controls indicated that the structure responsible for the postural and reflex changes was located in the dorsal pontine reticular formation, ventral to the LC.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Microinjections of GABAergic agents in the locus coeruleus modify the gain of vestibulospinal reflexes in decerebrate cats.

1. Precollicular decerebrate cats show a good postural activity in the four limbs and a small-amplitude vestibulospinal (VS) reflex, as revealed by recording the EMG response of the triceps brachii to sinusoidal roll tilt of the animal at 0.15 Hz, +/- 10 degrees. This preparation was used to study whether inactivation of the locus coeruleus (LC) elicited by local administration either of the GABA-A agonist muscimol or of the GABA-B baclofen produced changes in posture as well as in gain of the VS reflexes. 2. Microinjection into the LC of one side of 0.13-0.25 microliter of a muscimol or baclofen solution (at 2.5 or 1 microgram/microliter saline, respectively) stained with 5% pontamine, usually decreased the extensor tonus in the ipsilateral limbs and to a lesser extent also in the contralateral limbs. However, the amplitude of modulation and thus the gain of the first harmonic component of the multiunit EMG responses of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to the same parameters of labyrinth stimulation increased. The phase angle of the responses remained nearly unchanged by this treatment. The effects appeared 5-10 min after the injection of muscimol, fully developed in 30 min and progressively declined within the following 2-2.5 hours. 3. The increased gain of the VS reflexes acting on the triceps brachii did not depend on the decreased postural activity following the injection of the GABA-A or GABA-B agonist, since it was still observed if the reduced EMG activity following the injection was compensated by an increased static stretch of the muscle. Moreover, the postural and reflex changes described above were not due to irritative events following the injection, since they were not observed in control experiments following injection of 0.25 microliter saline within the LC-complex. On the other hand, postural and reflex changes opposite in sign to those elicited by muscimol or baclofen were obtained by local injection into the LC-complex of a GABA-A or GABA-B antagonist (0.25 microliter of bicuculline or faclofen at 8 micrograms/microliters saline). 4. In some experiments, the decrease in postural activity of the forelimbs after injection of muscimol into the LC complex was followed by transient episodes of postural atonia, which affected not only the ipsilateral but also the contralateral triceps muscles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled randomized trial in 80 patients.

Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and, therefore, whether it could be advocated as an adjunct to antiviral therapy.

Adult↗