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Biomedical subjects

G Jancsó

Publications and source records attributed to G Jancsó.

At least 37 records · Page 2Linked to original sources

RT97: a marker for capsaicin-insensitive sensory endings in the rat skin.

The mouse monoclonal antibody RT97, which recognises the 200-kDa neurofilament subunit in its phosphorylated form, selectively labels the somata of sensory A-fibres (large light cells) in the dorsal root ganglion of the rat. We have tested the hypothesis that this antibody also visualises large diameter sensory fibres and their end structures in peripheral tissue, in particular in the skin. RT97 immunoreactivity is found in endings that are known to be served by myelinated afferent fibres, including Meissner-like endings, Merkel discs, hair follicle receptors, Pacinian corpuscles and free nerve endings. RT97 immunoreactivity has not, however, been observed in endings of presumably unmyelinated sensory fibres (intraepidermal fibres immunoreactive for substance P and calcitonin gene-related peptide) or in sympathetic fibres innervating sweat glands and blood vessels. In addition, neither systemic (100-150 mg/kg as adults) nor perineural capsaicin pre-treatment affects RT97 immunoreactivity in the skin. The data indicate that RT97 is a useful marker in the study of the capsaicin-insensitive sensory innervation of the skin and possibly other peripheral organs.

Animals↗

Capsaicin treatment induces selective sensory degeneration and increased sympathetic innervation in the rat ureter.

Quantitative immunohistochemistry was used to study the innervation of the ureter in adult rats pretreated with capsaicin as neonates (50 mg/kg) or as adults (100-150 mg/kg, 10-22 days prior to being killed) using antibodies against protein gene-product 9.5, neuron-specific enolase, substance P, calcitonin gene-related peptide, neuropeptide Y, dopamine-beta-hydroxylase and vasoactive intestinal polypeptide. The number of calcitonin gene-related peptide- and substance P-containing fibres was reduced in the subepithelial plexus (adult capsaicin treatment < 1%, neonatal treatment < 5% of control), the submucosa (adult treatment < 11%; neonatal treatment < 51%) and in the smooth muscle layer and adventitia (adult treatment < 11%; neonatal treatment < 58%). Fibres immunoreactive for protein gene-product 9.5, a general neuronal marker, were reduced to 11% (adult treatment) or 0.5% (neonatal treatment) in the subepithelial plexus, but unchanged in the other layers, indicating a selective regional degeneration. In the smooth muscle layer the number of neuropeptide Y- and vasoactive intestinal polypeptide-containing nerve fibres was not altered by capsaicin. The number of neuropeptide Y fibres in the subepithelial plexus, however, was significantly increased after adult treatment (174% of control). After neonatal capsaicin treatment the intensity of the neuropeptide Y immunoreactivity was increased, more neuropeptide Y-positive nerve bundles were found and immunoreactive cell bodies were observed regularly in the adventitia of the ureter. The data indicate that capsaicin produces a selective degeneration of most afferent fibres in the subepithelial plexus of the rat ureter. This loss of capsaicin-sensitive afferent nerves evokes neuroplastic changes resulting in a hyperinnervation by neuropeptide Y-immunoreactive, presumably sympathetic fibres. The results suggest a mutual regulation of the pattern and density of innervation of peripheral target tissues by sensory and sympathetic neurons.

Animals↗

[Functional study of the regeneration of nerve fibers after keratinocyte transplantation].

The functional regeneration of sensory nerves was investigated in 5 patients with skin defects (caused by leg ulcers, a burn or fasciitis necrotisans) after transplantation with a keratinocyte suspension. In this area, first the pain sense and soon after wards the cold and heat sense returned, followed finally by the flare reaction caused by the mustard oil test. No sweat production could be observed during the study, because sweat glands were not found after the keratinocyte transplantation. The reinnervation course is roughly the same for skin defects covered with split skin graft or with a keratinocyte suspension.

Adult↗

Ruthenium red antagonism of capsaicin-induced vascular changes in the rat nasal mucosa.

Mechanisms of capsaicin-induced vascular changes were examined in the nasal mucosa of anesthetized adult rats. Intra-arterial infusions of capsaicin at doses of 20-100 pmol/min into the external carotid artery resulted in a dose-dependent increase in nasal blood flow as assessed by laser-Doppler flowmetry. Intra-arterial infusion of ruthenium red (RR, 2.5-10 mumol) prior to the administration of capsaicin significantly inhibited the capsaicin-evoked response. The technique of vascular labelling was used to examine nasal mucosal vascular permeability. Intravenous administration of colloidal silver solution prior to capsaicin infusion resulted in accumulation of colloid in the walls of small blood vessels, indicative of enhanced vascular permeability. Vascular labelling was largely abolished after RR pretreatment. These findings suggest that neuropeptides released from trigeminal sensory nerve endings play a significant role in the local vascular and inflammatory reactions of the nasal mucosa. The experimental approach utilized in this study provides a promising model for defining the roles of capsaicin-sensitive afferent nerves in the mechanisms of allergic and/or inflammatory diseases affecting the nasal mucosa.

Animals↗

A new technique for the direct demonstration of overlapping cutaneous innervation territories of peptidergic C-fibre afferents of rat hindlimb nerves.

A new technique based on the phenomenon of vascular labelling has been devised for the direct visualisation of overlapping innervation territories of cutaneous nerves. The saphenous, peroneal and sural nerves on one side in anaesthetised rats were exposed, cut centrally and successively stimulated antidromically to induce a neurogenic inflammatory response after an intravenous injection of either a 1% colloidal silver solution or a suspension of 3% Monastral Blue B. Light microscopic examination of transparent preparations of the dorsal hindpaw skin revealed labelled blood vessels of different colours which represented cutaneous territories served by different nerves. Blood vessels labelled with both substances were regarded as areas of overlapping innervation. Such areas were typically localised along the border of adjacent innervation territories. In addition, distinct areas exhibiting double-labelled blood vessels were regularly encountered in regions separate from this border zone. Areas of interest were drawn with the aid of a camera lucida and measured by means of a computerised system. The results indicate a significant, although topographically variable, degree of overlap of these cutaneous innervation areas. This new technique offers a possibility to explore the importance of normally existing overlap in the reinnervation of a denervated skin area by collateral nerve sprouting.

Animals↗

Possible involvement of capsaicin-sensitive sensory nerves in the regulation of cochlear blood flow in the guinea pig.

Capsaicin-induced microcirculatory changes in the cochlea of anaesthetized guinea pigs were examined by laser-Doppler flowmetry. Close intraarterial capsaicin infusion into the anterior inferior cerebral artery at doses of 10-50 pmol/min was followed by dose-dependent vasodilatation. Capsaicin infused in a dose of 150-200 pmol/min or above resulted in vasoconstriction in the region examined. Topical capsaicin administration into the cochlea (50-150 pmol) resulted in very moderate vasodilation with a latency of 1-2 min. Perivascular capsaicin application onto the anterior inferior cerebellar artery elicited an elevated blood flow in the cochlea, too. It is concluded that the release of vasoactive substances from capsaicin-sensitive nerve fibres in the inner ear of the guinea pig may play a role in the control of the local microcirculation. These nerves may also be involved in the neurogenic inflammatory processes in the region.

Animals↗

Naturally occurring deuterium is essential for the normal growth rate of cells.

The role of naturally occurring D in living organisms has been examined by using deuterium-depleted water (30-40 ppm D) instead of water containing the natural abundance of D (150 ppm). The deuterium-depleted water significantly decreased the growth rate of the L929 fibroblast cell line, and also inhibited the tumor growth in xenotransplanted mice. Eighty days after transplantation in 10 (59%) out of 17 tumorous mice the tumor, after having grown, regressed and then disappeared. We suggest that the naturally occurring D has a central role in signal transduction involved in cell cycle regulation.

Adenocarcinoma↗

Mustard oil-induced cutaneous inflammation in the pig.

Recent findings indicate that chemical stimulation of the porcine skin with capsaicin evokes a flare response similar to that observed in man. The aim of the present study was to elucidate whether chemical stimulation of cutaneous capsaicin-sensitive nerve endings with mustard oil produces neurogenic inflammatory reactions in the pig. The application of mustard oil onto the abdominal skin of domestic pigs resulted in a pronounced flare response. After a previous intravenous injection of a solution of Evans blue, the skin area in contact with the irritant turned dark blue, indicating a marked extravasation of albumin. Quantitative estimation of the dye content of the skin supported this conclusion. The technique of vascular labelling revealed a delicate network of small subepidermal blood vessels in histological preparations after the application of mustard oil following a previous intravenous injection of colloidal silver. Labelled blood vessels were not noted outside the treated area. The present results show that mustard oil produces a strong cutaneous inflammatory response in the pig, and suggest that the porcine skin provides a valuable model for study of the significance of capsaicin-sensitive sensory nerves in vascular and other cutaneous reactions.

Animals↗

Significance of the rate of systemic change in blood pressure on the short-term autoregulatory response in normotensive and spontaneously hypertensive rats.

Cerebral autoregulation, the physiological regulatory mechanism that maintains a constant cerebral blood flow (CBF) over wide ranges of arterial blood pressure, was investigated in normotensive and spontaneously hypertensive rats by means of laser-Doppler flowmetry. Systemic arterial hypertension was produced at rates ranging from 0.02 mm Hg/second to 11 mm Hg/second by constant infusion of epinephrine and norepinephrine. Systemic arterial hypotension was produced at rates ranging from -0.03 mm Hg/second to -12 mm Hg/second, either by bleeding the animals into a reservoir or by compressing the abdomen. In those cases with a low rate of change in systemic arterial blood pressure (SABP), the measurements lasted for 5 +/- 2 minutes, and in those with a high rate of change in SABP, measurements lasted for 40 +/- 30 seconds. The purpose was to record the time of onset and course of autoregulation in the basal ganglia in response to slow or rapid changes in SABP. CBF in the basal gray matter remained at baseline values (i.e., autoregulation was functioning) if the rate of increase of SABP did not exceed a critical value (0.10 mm Hg/second in the normotensive rats; 0.35 mm Hg/second in the spontaneously hypertensive rats). When hypertension was produced at faster rates, CBF followed arterial blood pressure passively, and no autoregulatory response was observed for 2 +/- 1 minutes. Hypotension did not change the baseline CBF when it was not produced at a rate faster than -0.4 mm Hg/second in normotensive rats and -0.15 mm Hg/second in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Appearance of diaminobenzidine-staining glial cells in the rat CNS: an ontogenetic histochemical study.

The postnatal appearance of diaminobenzidine (DAB)-staining glial cells was studied in certain regions of the rat central nervous system. DAB-positive cells appeared in the hypothalamus, the nucleus of the solitary tract and the most superficial laminae of the spinal dorsal horn on the 7th, 8th and 14th postnatal day, respectively. The number and staining intensity of these DAB-positive cells progressively increased and reached the adult levels at the end of the third postnatal week. Glial staining is likely to result from a non-enzymatic oxidation of DAB, since it was resistant to heat pretreatment, but was abolished if hydrogen peroxide was omitted from the incubation medium. The present results reveal that a particular population of glial cells exhibit a characteristic developmental change which can be detected by means of peroxidase histochemistry. The close topographical relationship is suggestive of a functional association between capsaicin-sensitive primary afferents and DAB-positive glial cells.

Animals↗

[Otoacoustic emission audiometry in neonates and adults].

The authors discuss the clinical use of the otoacoustic emission audiometry. During the physiological process of sound amplification in the cochlea vibration energy escapes from the inner ear. By the analysis of this sound it is possible to gain information about the function of the cochlea. According to the experiences of the authors the method is extremely useful for screening audiometry in pathological and normal neonates. In adults it can be used for monitoring the cochlear function during ototoxic therapy or noise exposure.

Adolescent↗

Pathobiological reactions of C-fibre primary sensory neurones to peripheral nerve injury.

Mammalian primary sensory neurones display profound anatomical and chemical changes in response to injury of their peripheral processes. Peripheral nerve damage results in transganglionic degeneration of central terminals of A-fibre primary afferent neurones terminating in the deeper layers of the medullary or spinal dorsal horn. The depletion of neuropeptides and other neurone-specific macromolecules from neurones in sensory ganglia and from the superficial dorsal horn, the known central projection area of C-fibre primary afferents, is a salient phenomenon commencing after peripheral nerve lesions. A recently devised new experimental procedure, termed the capsaicin-gap method, permitted evaluation of the transganglionic degenerative phenomena which develop in C-fibre primary sensory neurones after a lesion is inflicted upon their peripheral branches. The experimental findings indicated that C-fibre primary afferent terminals underwent transganglionic degeneration following a perineural treatment with capsaicin, and that this was associated with, and probably resulted from, ganglionic cell degeneration. Studies on the effects of peripheral nerve section yielded similar results. It has therefore been suggested that the observed depletion of specific macromolecules, including sensory peptides, specific glycoconjugates and sensory neurone specific acid phosphatase, may be accounted for, at least in part, by an irreversible loss of sensory ganglion neurones. In contrast, many injured neurones express peptides, including vasoactive intestinal polypeptide, peptide histidine-isoleucine and galanin, which can be demonstrated in only a few neurones under normal conditions. These seem to be involved in dorsal horn regenerative and/or compensatory processes following peripheral nerve damage. There is suggestive evidence that the partial deafferentation caused by the transganglionic degeneration of C-fibre primary afferents creates favourable circumstances for an anatomical rearrangement of neuronal connections within the spinal cord dorsal horn. These changes may provide a morphological substrate of some of the functional alterations demonstrated after peripheral nerve lesions.

Animals↗

Possible morphological correlates of capsaicin desensitization.

The changes in the fine structure of axonal profiles of the guinea-pig ureter were examined after exposure to capsaicin in vitro. In the ureters exposed to capsaicin (1-10 microM), about 60%, of all axonal profiles exhibited conspicuous ultrastructural impairment. It is suggested that these alterations might interfere with the release of peptides from these particular nerve endings and therefore contribute significantly to the mechanisms of capsaicin desensitization.

Animals↗

Ruthenium red inhibits tail skin vasodilatation evoked by intracerebroventricular injection of capsaicin in the rat.

The effect of Ruthenium red on the tail skin vasodilatation evoked by an intracerebroventricular injection of capsaicin was studied in the anesthetized rat. Injection of capsaicin into the lateral ventricle resulted in a marked elevation of the tail skin temperature, indicative of peripheral vasodilatation. Ruthenium red, given by intracerebroventricular injection, significantly inhibited this response, which is known to be mediated by central warmth-sensitive neuronal structures. The findings suggest that the sensitivity to Ruthenium red, reportedly characteristic of the capsaicin-sensitive neurons in the peripheral nervous system, is also a trait of the capsaicin-sensitive nerve cells in the central nervous system. This is the first evidence indicating that similar molecular mechanisms, presumably involving changes in cellular calcium metabolism, contribute to the capsaicin-induced activation of neurons in both the peripheral and central nervous systems.

Animals↗

A possible pathomechanism of the idiopathic cold contact urticaria.

Urtica is characterized by an erythematous wheal surrounded by a flare and is frequently caused by physical agents (e.g. cold). The exact mechanism and mediators involved in the mechanism of physical urticaria are not known. This study of the role of the neurogenic factors in cold urticaria showed, that local capsaicin treatment (desensitization) of the skin in patients with cold urticaria resulted in the abolition of whealing in response to cold. This result suggests that C-fibers might play an important role in the pathomechanism of idiopathic contact cold urticaria.

Adult↗

Transganglionic degeneration of capsaicin-sensitive C-fiber primary afferent terminals.

Local treatment of rat peripheral nerves with capsaicin induces permanent impairment of afferent C-fiber functions and changes in the response properties of spinal dorsal horn neurons. In this study a new experimental approach, the "capsaicin gap" technique, has been utilized in an attempt to unravel pathomorphological alterations which commence in the domain of primary sensory neurons as a consequence of perineural treatment with capsaicin. The technique relies on the facts that peripheral nerves in the spinal dorsal horn are represented in a strict somatotopic manner, and on the observation that in the adult rat systemic injection of appropriate doses of capsaicin results in a selective degeneration of primary afferent fibers within Rexed's laminae I and II of the spinal cord. We have assumed that, if treatment of a peripheral nerve with capsaicin results in an irreversible destruction of primary afferent terminals related to that nerve, then the corresponding spinal projection areas will be free of degeneration following a subsequent systemic injection of capsaicin. The topographical distribution of degenerating axon terminals, induced by a systemic injection of capsaicin, was studied within the lumbar spinal cord of rats whose sciatic nerves had been treated with capsaicin or its vehicle one to three months previously. In the dorsal horn ipsilateral to the vehicle-treated nerve, axon terminal degeneration was found in the entire mediolateral extent of Rexed's laminae I and II. In contrast, in the dorsal horn ipsilateral to the capsaicin-treated nerve, virtually no degeneration was observed in areas which correspond to the projection territories of sciatic afferents. It is concluded that the central terminals of capsaicin-sensitive sciatic afferents underwent transganglionic degeneration as a result of prior perineural treatment with capsaicin, and a subsequent systemic injection of this neurotoxin therefore failed to cause axon terminal degeneration in somatotopic areas served by the treated nerve. Comparative quantitative morphometric analysis of cell populations of dorsal root ganglia related to capsaicin- or vehicle-treated nerves disclosed (1) a marked reduction in the proportion of small-sized neurons, (2) a fall of about 80% in the percentage of neurons which undergo degeneration after the systemic injection of capsaicin, and (3) a marked decrease in the total number of neurons in ganglia ipsilateral to the capsaicin-treated nerves. Quantitative electron microscopic studies on saphenous nerves treated perineurally with capsaicin revealed a 32% reduction in the number of unmyelinated axons as compared with the controls, whereas the number of myelinated fibers was unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Treatment of severe hyaline membrane disease with surfactant (Curosurf). A collaborative clinical study.

We investigated the clinical efficacy of a new surfactant product, Curosurf, isolated from porcine lungs by liquid-gel chromatography. Ten premature newborn infants (birth weight 850-1850 g), all ventilated artificially for severe hyaline membrane disease categorized radiologically as stage III-IV, received a single dose of Curosurf (200 mg/kg) via the tracheal tube. This treatment resulted in a rapid improvement of oxygenation, similar to that observed by other teams collaborating in the study and, in an astonishingly fast resolution of the radiological changes. In comparison with a control group of 8 infants, the surfactant-treated babies also had a lower incidence of acute and chronic complications.

Biological Products↗

Topical versus systemic capsaicin desensitization: specific and unspecific effects as indicated by modification or reflex micturition in rats.

The aim of this study was to determine the acute and delayed effect of topical application of high concentrations of capsaicin on the rat urinary bladder on micturition reflex and compare the effects of "topical" bladder desensitization with those produced by systemic (subcutaneous administration) capsaicin desensitization. On acute application, capsaicin (1-3%) produced a transient bladder contraction, not observed in capsaicin-pretreated rats. After a transient increase in excitability of the micturition reflex, topical capsaicin suppressed micturition and overflow incontinence ensued which was reverted by intravenous injection of 4-aminopyridine. Topical capsaicin also abolished reflex micturition in rats which had been systemically treated with capsaicin as adults (50 mg/kg, 7 days before) and reduced significantly the neurogenic bladder contractions produced by intravenous dimethylphenylpiperazinium or neurokinin A, while the direct (myogenic) response to neurokinin A was unaffected. In rats whose bladder was pre-exposed to 1-3% topical capsaicin (7 days before) the micturition reflex was affected in a manner which is qualitatively and quantitatively similar to that observed in rats treated with capsaicin as adults, e.g. increase in bladder capacity with no change in voiding efficiency. Topical capsaicin desensitization of the rat urinary bladder was shown to produce a selective impairment of bladder sensory nerves without any sign of desensitization in other areas of the body using both functional (hot plate, wiping, plasma extravasation) and neurochemical (determination of substance P-like immunoreactivity) assays. Systemically administered capsaicin (7 days before) had little effect on reflex micturition at 12.5 mg/kg but the change in bladder capacity produced at a dose of 25 mg/kg was comparable with that produced at 350 mg/kg. These findings provide evidence that selective desensitization of peripheral terminals of capsaicin-sensitive nerves of the rat urinary bladder inactivates their sensory and "efferent" function in a manner similar to that observed after systemic capsaicin desensitization in adult rats. The functional deficit of reflex micturition produced in this way can be overcome by increasing the stimulus to void. By contrast, neonatal capsaicin desensitization produced a long lasting abolition of reflex micturition. These data are in keeping with the hypothesis that adult versus neonatal capsaicin desensitization may be used as a tool to distinguish between two sets of sensory nerves in the rat urinary bladder.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗