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Biomedical subjects

G Benedek

Publications and source records attributed to G Benedek.

At least 19 recordsLinked to original sources

Antinociceptive effects of the hydrophilic alpha 2-adrenoceptor agonist ST-91 in different test circumstances after intrathecal administration to Wistar rats.

The antinociceptive and motor effects of the hydrophilic alpha 2-adrenoceptor agonist ST-91 were studied after intrathecal administration to male Wistar rats in different heat-pain tests and different test settings. Intrathecal administration of ST-91 caused a dose-dependent increase in hind paw licking latency in the hot-plate test, while in contrast with morphine it had a much lower efficacy in the tail-flick test in freely moving conditions. Sprague-Dawley rats gave similar results to those for Wistar rats in this setting. However, when the tail-flick test was performed under chronic restraint conditions (after a 1-h restraining period), the compound caused a significant antinociception. No signs of motor impairment and no changes in electromyographic activity were detected after ST-91 administration. The results indicate a characteristic analgesic profile for ST-91. In the interpretation of ST-91 data, consideration should be paid both to test model differences and to test conditions.

Adrenergic alpha-2 Receptor Agonists

Visual, somatosensory, auditory and nociceptive modality properties in the feline suprageniculate nucleus.

Response properties of 252 single-units to visual, auditory, somatosensory and noxious stimulation were recorded by means of extracellular microelectrodes in the suprageniculate nucleus of anaesthetized, immobilized cats. Of the 141 units tested for modality properties the majority (n=113, 80.1%) was found unimodal in the sense that stimuli of exclusively one sensory modality were able to elicit an activation of the unit. Twenty-four (17.0%) cells were bimodal and four (2.8%) were trimodal (visual, somatosensory and auditory). The visual modality dominated the unimodal cells (n=74, 65.5%), while cells responsive to somatic stimulation (n=20, 17.6%), auditory stimulation (n=16, 14.1%) or noxious stimulation of the tooth pulp (n=3, 2.6%) were less frequently encountered. Visual sensitivity dominated the multisensory cells, too. The visually responsive units were characterized by having a sensitivity to stimuli moving in a rather large, uniform receptive field that covered the contralateral lower quadrant, and encompassed a flanking area of about 20 degree width in both the upper contralateral and lower ipsilateral visual fields. Many cells (n=52, 47%) were sensitive to the direction of the stimulation and reacted to stimuli moving at a high velocity (20-200 deg/s). Most cells responded differently to stimuli of a variety of sizes. Somatosensory units reacted to stimuli presented over a wide area on the contralateral side of the body, thus showing no sign of somatotopic organization. The auditory sensitivity fell within a wide range of acoustic stimuli in extremely large auditory receptive fields. The physiological properties of suprageniculate nucleus cells strongly resemble the sensory properties of cells found along the ventral bank of the anterior ectosylvian sulcus and the deeper layers of the superior colliculus. Our results provide further support for the notion of a separate tecto-suprageniculate-anterior ectosylvian sulcus/insular pathway that takes part in the processing of multimodal signals important for various types of sensory related behaviours.

Acoustic Stimulation

Mechanisms of within- and cross-modality suppression in the superior colliculus.

The present studies were initiated to explore the basis for the response suppression that occurs in cat superior colliculus (SC) neurons when two spatially disparate stimuli are presented simultaneously or in close temporal proximity to one another. Of specific interest was examining the possibility that suppressive regions border the receptive fields (RFs) of unimodal and multisensory SC neurons and, when activated, degrade the neuron's responses to excitatory stimuli. Both within- and cross-modality effects were examined. An example of the former is when a response to a visual stimulus within its RF is suppressed by a second visual stimulus outside the RF. An example of the latter is when the response to a visual stimulus within the visual RF is suppressed when a stimulus from a different modality (e. g., auditory) is presented outside its (i.e., auditory) RF. Suppressive regions were found bordering visual, auditory, and somatosensory RFs. Despite significant modality-specific differences in the incidence and effectiveness of these regions, they were generally quite potent regardless of the modality. In the vast majority (85%) of cases, responses to the excitatory stimulus were degraded by >/=50% by simultaneously stimulating the suppressive region. Contrary to expectations and previous speculations, the effects of activating these suppressive regions often were quite specific. Thus powerful within-modality suppression could be demonstrated in many multisensory neurons in which cross-modality suppression could not be generated. However, the converse was not true. If an extra-RF stimulus inhibited center responses to stimuli of a different modality, it also would suppress center responses to stimuli of its own modality. Thus when cross-modality suppression was demonstrated, it was always accompanied by within-modality suppression. These observations suggest that separate mechanisms underlie within- and cross-modality suppression in the SC. Because some modality-specific tectopetal structures contain neurons with suppressive regions bordering their RFs, the within-modality suppression observed in the SC simply may reflect interactions taking place at the level of one input channel. However, the presence of modality-specific suppression at the level of one input channel would have no effect on the excitation initiated via another input channel. Given the modality-specificity of tectopetal inputs, it appears that cross-modality interactions require the convergence of two or more modality-specific inputs onto the same SC neuron and that the expression of these interactions depends on the internal circuitry of the SC. This allows a cross-modality suppressive signal to be nonspecific and to degrade any and all of the neuron's excitatory inputs.

Acoustic Stimulation

Why laparoscopic cholecystectomy today?

Traditional open cholecystectomy became the "gold standard" of surgical treatment for symptomatic gallstone disease during the last century. In spite of its good results, clinicians have been trying to establish effective nonsurgical methods of eliminating gallstones. Although oral, percutaneous, or retrograde litholysis can be used effectively for cholesterol stones, these represent only 10% of all gallstones. Moreover, intracorporeal lithotripsy is an invasive method, and while extracorporeal shock wave lithotripsy is a promising procedure, even after careful selection, only 70%-80% of the patients become stone-free within 1 year. In fact, none of the methods which leave the gallbladder intact are free of complications, and they are followed by 50% stone recurrence within 5 years. Since 1987, laparoscopic cholecystectomy has become the procedure of choice as it is safe and only minimally invasive. We believe that the laparoscopic technique is a promising way to the surgery of the future.

Bile Acids and Salts

Visual, somatosensory and auditory modality properties along the feline suprageniculate-anterior ectosylvian sulcus/insular pathway.

Physiological properties of single units were investigated in the suprageniculate nucleus (SG) and in the cerebral cortex along the anterior ectosylvian sulcus (AES), including the insular cortex. The recording was performed with the aid of carbon-filled glass micropipetts in barbiturate-anesthetized cats. The main findings of the study can be summarized as follows. 1. The physiological properties of the cells in the suprageniculate nucleus and in the AES/insular cortex exhibited striking similarities in a series of aspects: (a) The frequencies of occurrence of uni-, bi- and trimodal cells were similar. (b) The majority of the unimodal cells (75% in the AES/insular region and 65% in the SG) has visual sensitivity in both structures. The bimodal and trimodal cells were also dominated by visual sensitivity. (c) The somatosensory and auditory modalities were similarly present in both structures, although less frequently than the visual one. (d) No systematic topological organization was found in either structure. (e) The visual, somatosensory and auditory receptive fields were uniform and covered a fairly large proportion of the personal space. 2. Statistical comparison of some physiological properties of cells situated deep in the AES with those of cells in the insular cortex revealed differences as follows: (a) The insular cortex contained significantly more bi- and trimodal cells than the sulcal areas. (b) Cells in the insular cortex preferred significantly lower stimulus velocities and larger stimuli than cells in the depths of the AES. These results seem to support the notion of a suprageniculate-AES/insular thalamo-cortical multisensory entity. Additionally, the physiological differences between the sulcal AES cortex and gyral insula are in agreement with the morphological differences found earlier in the afferentation of these areas (Norita et al., 1986, 1991).

Animals

Human oscillatory potentials: components of rod origin.

Oscillatory potentials (OPs) evoked by white flashing light after dark or light adaptation (WDA and WLA conditions) and those evoked by blue flashing light stimulation against a dark background (BDA condition) were recorded in 16 healthy volunteers. When blue flashing light was employed over a scotopic background, the two major OPs of this response (OP2 and OP3) appeared with a latency time that sharply coincided with the third (OP3) and fourth (OP4) components of the OPs evoked by white flashes. The results provide evidence in support of the notion that various elements of OPs represent the activities of different retinal mechanisms, of which OP3 and OP4 seem to be of rod origin.

Adolescent

Oxidation of gamma II-crystallin solutions yields dimers with a high phase separation temperature.

Aqueous solutions of the bovine eye lens protein gamma II (or gamma B)-crystallin at neutral pH show a gradual increase in phase separation temperature, Tph, when allowed to stand for several weeks at room temperature without reducing agents. In a typical experiment, the Tph of the protein solution (218 mg/ml) increases from 2.5 +/- 1 degree C to 32.5 +/- 1 degree C after 21 days, and a new protein species, gamma IIH, is formed. The Tph of pure gamma IIH is at least 40 degrees C higher than that of pure gamma II. The average apparent hydrodynamic radius is 36 A for gamma IIH compared to 26 A for gamma II. The molecular mass of gamma IIH is approximately 41.5 kDa compared to 20 kDa for native gamma II. Therefore, gamma IIH is probably a dimer of gamma II crystallin. gamma IIH has a lower thiol content than gamma II and is not formed in the presence of dithiothreitol. We conclude that gamma IIH is a thiol oxidation product of gamma II-crystallin and is a dimer containing an intermolecular disulfide crosslink. Thus, some oxidative modifications of protein thiol groups lead to an increase in net attractive interactions between proteins. As a result, Tph increases and protein aggregates are formed. These two microscopic changes produce the increased light scattering associated with lens opacification.

Animals

Organization of the colliculo-suprageniculate pathway in the cat: a wheat germ agglutinin-horseradish peroxidase study.

A wheat germ-agglutinated horseradish peroxidase (WGA-HRP) tracing technique was used to label the cell bodies of neurons in the superior colliculus that send projections into the visually sensitive region of the suprageniculate nucleus (Sg) in the feline thalamus. After determination of the position of the Sg by detecting characteristic single-unit responses to moving visual stimuli, WGA-HRP was injected into the Sg in five pentobarbital-anesthetized cats. The animals were than sacrificed, and serial frozen sections of the midbrain were processed for the demonstration of peroxidase activity. A total of 2,736 WGA-HRP-stained neurons were located within the ipsilateral superior colliculus (SC), and a few labeled cells were consistently found bilaterally in the external nuclei of the inferior colliculus. In each cat, a small but significant fraction of the labeled cells were encountered contralateral to the injection. Medial SC neurons tended to project to the posterior Sg, and lateral SC neurons tended to project to more rostral Sg. However, labeled cells were distributed homogeneously along the rostrocaudal extent of the SC, indicating the absence of a well defined topographic relationship. Nor was the Sg injection site location related to the laminar distribution of SC projection neurons. In all cases, the majority of the labeled cells were found in layer IV (49.0%), with fewer cells in layers III (17.5%) layer V (20.0%), and layer VI (11.8%). No labeled cells were located in layer I, although a few were located in the deep part of layer II. Five types of SC projection cells were distinguished morphologically. Of the 258 labeled cells that could be characterized, 25% were stellate cells, 25% vertical cells, 20% granular cells, 17% triangular cells, and 12% horizontal cells. The average diameter of 226 cells ranged between 8 and 47 microns. We conclude that a mixed population of SC cells projects to the Sg; the morphological heterogeneity and the distribution of these cells suggests that several functionally different pathways may be involved in the colliculothalamic pathway and in the processing of visual input in the SC.

Animals

Bilateral projections from the superior colliculus to the suprageniculate nucleus in the cat: a WGA-HRP/double fluorescent tracing study.

Following WGA-HRP injection into the right suprageniculate nucleus of the cat brain, retrogradely-labeled neurons were found not only in the ipsilateral, but also in the contralateral superior colliculi. After WGA-HRP injection into the unilateral superior colliculus, anterogradely-labeled axon terminals were observed in the bilateral suprageniculate nuclei, and electron microscopic examination revealed that these were large terminals which made asymmetric synaptic contacts with dendrites. When a different kind of fluorescent tracer was injected into each suprageniculate nucleus (Fast blue and Nuclear yellow), double-labeled neurons were observed in the rostral and middle portions of both superior colliculi. These results suggest that there are direct bilateral projections from the superior colliculus to the suprageniculate nuclei, and that some of these projections originate from branching colliculo-suprageniculate axons.

Animals

Mydriatic and antinociceptive effects of intrathecal dexmedetomidine in conscious rats.

A comparison was made of the dose-effect relationship of intrathecally applied dexmedetomidine as concerns its mydriatic and antinociceptive effects in rats. Pupil diameter was measured with a photographic method without anesthesia. Antinociception was measured by means of the tail-withdrawal test. The intrathecal (i.t.) administration of dexmedetomidine led to dose-dependent antinociception (P < 0.05) and mydriasis (P < 0.001). Both effects reached their maximum 10 min after drug application. The tail-withdrawal latency was prolonged by 9 micrograms dexmedetomidine. Mydriasis appeared on administration of a 1 microgram dose and its degree was proportional to the dexmedetomidine dosage up to 12 micrograms. A significant correlation was not found between pupil diameter and tail-withdrawal latency in the same rat after any dexmedetomidine dose. Based on the present experiments, we conclude that the mydriatic effect of i.t. dexmedetomidine appears at a lower dose than its antinociceptive effect. Our results suggest that the assessment of pupillary response is a sensitive method for estimation of the supraspinal effect of i.t. administered alpha 2-adrenoceptor agonists.

Adrenergic alpha-Agonists

Electrophysiologic alterations in patients with optic nerve hypoplasia.

The clinical and electrophysiologic data (electroretinograms and visual evoked potentials) were studied in 45 patients with optic nerve hypoplasia. The patients were divided into three fairly distinct groups on the basis of their electrophysiologic alterations. Group 1 consisted of 13 patients with almost extinguished visual evoked potentials and with mild electroretinographic alterations. These were the cases that are traditionally recognized as optic nerve hypoplasia. The serious visual impairment in these cases was accompanied by various developmental ophthalmologic and nonophthalmologic abnormalities. Group 2 included 26 patients without any significant visual evoked potential or electroretinographic alterations, but with overt funduscopic signs of optic nerve hypoplasia. These patients were consistently suffering from strabismus and/or amblyopia. The visual functions based on visual evoked potential and electroretinographic recordings could be fairly normal apart from a pathologic ophthalmoscopic picture characteristic of optic nerve hypoplasia. Group 3 included six patients with abnormal albeit well-recordable visual evoked potentials and subnormal or negative-type electroretinograms that suggested an accompanying retinal disease. This finding seems to prove that a subset of patients with optic nerve hypoplasia with nystagmus may have a primary retinal abnormality. Our study provides further evidence that optic nerve hypoplasia is not a uniform disease entity.

Adolescent

An ultrasonographic method for the evaluation of dexmedetomidine on micturition in intact rats.

We describe a simple, noninvasive, nontraumatic, and reproducible ultrasonographic method to determine the effect of the alpha 2-adrenoceptor agonist dexmedetomidine in anesthetic dose (300 micrograms/kg subcutaneously) on the micturition reflex in intact rats. The bladder volumes were estimated by an ellipsoid equation. To validate the reliability of the method, an in vitro model assessment also was performed. The mean difference between estimated and instilled volumes were 27.3 microL (-21.61, 76.23). The highly significant correlation (r = 0.98, p < .001) indicates that the ultrasonography with the equation is a reliable tool. After the dexmedetomidine administration to intact rats, urine dribbling occurred at 30 +/- 4.8 min. The volume threshold for urination was 2100 +/- 100 microL. Although dribbling of the urine was observed almost continuously, significant differences were not observed between bladder volumes obtained at any time (from 10 to 100 min). This study indicates that the alpha 2-adrenoceptor agonist dexmedetomidine inhibits the micturition reflex in intact rats. The method described, which is both noninvasive and nonpainful, may therefore be widely used to quantify in small animals pharmacological effects on the urinary bladder.

Animals

Suppression of phase separation in bovine gamma IV crystallin solutions: effect of modification by charged versus uncharged polar groups.

gamma IVa Crystallin, the ocular lens protein with the highest critical temperature (Tc) for phase separation, has been chemically modified with N-ethylmaleimide (NEM) at neutral pH. NEM, a polar but uncharged modifier reacts with the cysteine residues of the protein. A maximum of 80-85% of the thiol groups are modified and the phase separation temperature is lowered by about 10 degrees C at a protein concentration of 30 mg ml-1. The coexistence curve of the NEM-modified protein with nearly four out of the six cysteines modified was determined and compared with that obtained by modifying the protein with a charged reagent, N-bromoacetylethanolamine phosphate (NBAEP). NBAEP modifies both cysteine and methionine residues of gamma IVa crystallin. The results of these two modification studies indicate that for the same total degree of modification of the sulfur-containing residues, the suppression in Tc due to the charged NBAEP is at least twice as large as that due to the polar but uncharged NEM. In order to obtain some measure of the relative hydrophilicities of the two modifiers, we have estimated the free energies of hydration of the nonionic segments of NEM and NBAEP, using structural additivity schemes. We find that the intrinsic hydrophilicities of the nonionic segments of these two modifiers are nearly equal. Hence the much larger suppression of Tc resulting from NBAEP modification is most probably due to the strongly polar, doubly charged phosphate group.

Amino Acids

Dexmedetomidine-induced decrease in cerebral blood flow is attenuated by verapamil in rats: a laser Doppler study.

This study was performed to examine the changes in local cortical blood flow (CoBF) after simultaneous administration of an alpha 2 adrenergic agonist (dexmedetomidine) and a calcium channel antagonist (verapamil) to urethane-anaesthetized rats. Dexmedetomidine (100 micrograms.kg-1) given intraperitoneally alone resulted in decreases in mean arterial blood pressure (MABP) (F[27,140] = 3.43; P < 0.01) and CoBF (F[27,140] = 4.22; P < 0.01), whereas the heart rate (HR) was increased (F[27,140] = 2.33; P < 0.01). Verapamil (2.5 mg.kg-1) given subcutaneously reduced the MABP (F[27,140] = 3.41; P < 0.01), but the HR and CoBF were not changed. Combined administration of the drugs decreased MAPB (F[27,140] = 5.37; P < 0.01), with no changes in CoBF and HR. The present data indicate that the calcium channel antagonist verapamil did not potentiate the haemodynamic effects of dexmedetomidine in rats, but rather attenuated the effect of dexmedetomidine on CoBF. This favourable interaction suggests a potential therapeutic role of these agents in maintaining cardiovascular stability during surgical interventions.

Adrenergic alpha-Agonists

Spatial selectivity in the anterior ectosylvian visual area of the cat.

Pattern reversal visually evoked potentials (PR-VEPs) were recorded in the anterior ectosylvian visual area (AEV) of the cat, and the dependence of the PR-VEPs on the spatial frequency (SF) and the mean luminance of the stimulation was studied. Six SFs between 0.025 and 1 cycles per degree (c/d) and four light density levels between 2 x 10(-2) and 117 cd/m2 (candela per square meter) were tested. The latency of the first positive component (P1) and the amplitude measured between P1 and the first negative (N1) component were analyzed. The dependence of the PR-VEP latencies on the SF displayed a significant relationship, with a minimum at around 0.05 c/d. This relationship was consistent at all luminance levels tested. The dependence of the amplitudes on the SF gave a "low-pass" tuning curve at every luminance level. The higher the luminance level, the steeper was the curve. The cut-off SF of these curves was at around 1 c/d under photopic conditions and around 0.6 c/d under scotopic conditions. The contrast dependence of the PR-VEP amplitudes exhibited saturation at 0.5, which was much higher than that of either the striate cortex or other extrastriate visual cortical areas, but similar to that of the superior colliculus. These results provide further evidence in support of the notion of a tecto-extrageniculo-extrastriate visual pathway functioning separately from the geniculo-striate mechanisms.

Animals

Visual evoked potentials during the early phase of optic nerve compression in the orbital cavity.

We obtained case histories and electrophysiologic recordings from four patients with transient vision impairment due to acute orbital compression. The visual evoked potentials (VEPs) displayed alterations that depended on the size and consistency of the compressing pathology and also on the duration of the compression. This study provides evidence of the utility of the VEP in the assessment of the severity and reversibility of optic nerve lesions. The case histories also emphasized the necessity to elucidate the pathologic process of compressive lesions of the optic nerve.

Acute Disease

An isobolographic analysis of the hypnotic effects of combinations of dexmedetomidine with fentanyl or diazepam in rats.

The effects of the combinations of dexmedetomidine-fentanyl and dexmedetomidine-diazepam on the righting reflex were studied in rats. The doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. The interactions between dexmedetomidine and fentanyl or diazepam were found to be synergistic. In the dexmedetomidine-diazepam combination studies, less than one-fourth of the single drug dose (for each of two agents) was needed to produce the required effect. These data confirm synergistic interactions between dexmedetomidine and fentanyl or diazepam in producing hypnotic-anesthetic action.

Anesthetics

Potentiated hypnotic action with a combination of fentanyl, a calcium channel blocker and an alpha 2-agonist in rats.

An investigation was made of the hypnotic-anaesthetic effects in rats of subcutaneous coadministration of fentanyl (25-100 micrograms.kg-1), clonidine (100-300 micrograms.kg-1) and verapamil (1-5 mg.kg-1). Hypnotic-anaesthetic efficacy was assessed via loss of the righting reflex. In the doses used, none of the three drugs alone was associated with appreciable hypnotic-anaesthetic effects. Coadministration of fentanyl and clonidine resulted in a dose-related enhancement of the anaesthetic potency, without change in the duration of hypnotic action. Verapamil coadministration failed to increase the anaesthetic efficacy of binary combinations of fentanyl and clonidine, but a marked prolongation of the duration of hypnotic action was observed (P less than 0.001). These results suggest the existence of unreported interactions between these three drugs in the production of hypnotic-anaesthetic action in rats.

Adrenergic alpha-Agonists