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Biomedical subjects

E Verdú

Publications and source records attributed to E Verdú.

17 recordsLinked to original sources
PubMed1999

Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy.

Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for calcitonin gene-related peptide (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents.

Animals↗
PubMed1998

Changes in cholinergic responses of sweat glands during denervation and reinnervation.

Functional sudomotor responses have been studied in sweat glands reinnervated after sciatic nerve crush and partially denervated by cisplatin intoxication in the mouse. The sudomotor function mediated by the sciatic nerve was evaluated by silicone imprints on the plantar surface of the hindpaws. Five days after nerve crush, completely denervated sweat glands became unresponsive to cholinergic stimulation with pilocarpine. During the following weeks, the number of reinnervated, reactive sweat glands increased progressively to reach a maximum of 89% of preoperative control counts by 40 days after nerve crush. At this time, the mean volume of sweat secreted per gland was normal, but reinnervated glands showed a secretory activity abnormally sustained over time after pilocarpine stimulation and, on the other hand, had an increased resistance to the inhibition of secretion induced by atropine. The effects of cisplatin administration on sudomotor function were investigated in two groups of mice, one treated with high doses of cisplatin (10 mg/kg/week for 4 weeks) and another treated with low doses of cisplatin (5 mg/kg/week for 8 weeks). Cisplatin intoxication produced abnormal sudomotor responses indicative of denervation from cumulative doses of 10 mg/kg. The first abnormality found was a partial resistance of sweat glands to atropine, followed by a decrease in the sweat output per gland and finally a decline in the number of sweat glands activated by pilocarpine. These abnormalities in the sudomotor responses were more pronounced in mice treated with a high dose than in those with a lower dose regime.

Animals↗
PubMed1997

Immunohistochemical study of skin reinnervation by regenerative axons.

The time sequence of sensory and sudomotor nerve regeneration to the mouse footpad was studied between one and seven weeks after crush or section of the sciatic nerve. Protein gene product 9.5, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide were localized in thick sections by using indirect immunofluorescence techniques and imaged by confocal microscopy. Nerve regeneration was visually assessed in all nerves and quantified in sweat glands. After denervation, protein gene product 9.5 immunoreactivity remained as dim fluorescence within thick fibers of dermal nerve trunks, whereas thin nerve fibers to sweat glands and to epidermis disappeared. By 14 days postcrush and 35 days postsection, the first protein gene product 9.5 immunoreactive regenerating axons appeared in large nerve trunks, quickly extending to epidermis and sweat glands. Reinnervation of Meissner's corpuscles occurred nearly simultaneous with return of epidermal free nerve endings and sudomotor network. Calcitonin gene-related peptide, vasoactive intestinal peptide, and substance P immunoreactivity disappeared completely one week after denervation, then reappeared at 17-18 days postcrush and 35 days postsection. Fewer nerve fibers were immunoreactive to these peptides than to protein gene product 9.5. The overall density of reinnervation, although reduced, more closely resembled normal in the sweat glands and Meissner's corpuscles than in the epidermis. Reinnervation was more successful after crush than after nerve section. The time course for functional return of sweating paralleled the return of protein gene product 9.5 immunoreactivity, whereas appearance of vasoactive intestinal peptide was delayed by several days.

Animals↗
PubMed1997

Effect of curing Helicobacter pylori infection on intragastric acidity during treatment with ranitidine in patients with duodenal ulcer.

BACKGROUND: In patients with duodenal ulcer cure of Helicobacter pylori infection resulted in a pronounced decrease in intragastric pH during treatment with omeprazole. AIM: To test the hypothesis that treatment of H pylori adversely affects the pH response to ranitidine. PATIENTS: Eighteen patients with duodenal ulcer who were infected with H pylori were studied. METHODS: Twenty four hour pH recordings were performed during treatment with ranitidine (300 mg) at night before and four to six weeks after cure of H pylori infection. Presence of H pylori was assessed by a rapid urease test, culture, histology, and a 13C urea breath test. Also, the fasting gastrin concentrations were measured before and after treatment for H pylori infection. RESULTS: Cure of H pylori infection resulted in a considerable improvement in both antral and corpus gastritis and a decrease in fasting gastrin concentrations. As a result of the cure the night time intragastric pH during treatment with ranitidine decreased (median pH 6.8 v 5.4; p = 0.007), whereas the acidity during the daytime was not affected. CONCLUSIONS: In patients with duodenal ulcer the intragastric pH during treatment with ranitidine depends on H pylori. However, the loss of effectiveness in altering pH seems to be less pronounced than previously found with omeprazole.

Adult↗
PubMed1997

Efficacy of omeprazole one year after cure of Helicobacter pylori infection in duodenal ulcer patients.

OBJECTIVE: We have previously shown that, in duodenal ulcer patients, pH control by omeprazole is less pronounced after cure of Helicobacter pylori infection. The present study was designed to test the hypothesis that this response to omeprazole persists 1 yr after cure of H. pylori infection. METHODS: In 12 duodenal ulcer patients, intragastric acidity was measured with a glass electrode during treatment with omeprazole (20 mg) once daily before, and 4-6 wk and 1 yr after, cure of H. pylori infection. H. pylori infection was assessed by [13C]urea breath test, culture, histology (Warthin Starry stain), and rapid urease test. RESULTS: Cure of H. pylori infection resulted in a lowered pH during omeprazole treatment. This effect persisted after 1 yr. Median 24-h gastric pH before H. pylori treatment was 5.6; 4-6 wk after cure of the infection it was 2.9 (p = 0.003), and 1 yr after cure of the infection it remained unchanged (pH = 2.5; p = 0.5). Accordingly, twice as much time was spent above pH 3 and pH 4 before H. pylori treatment than 1 or 12 months after cure (percent of time > or = pH 3: 82.7 vs. 49.7 vs. 43.1; percent of time > or = pH 4: 72.7 vs. 38.3 vs. 26.4). CONCLUSION: In duodenal ulcer patients, cure of H. pylori infection resulted in a marked rapid and persistent decrease of the pH increasing effect of omeprazole. Therefore, H. pylori is a determinant of the pH achieved in response to omeprazole treatment in duodenal ulcer patients.

Adult↗
PubMed1996

Influence of physical parameters of nerve chambers on peripheral nerve regeneration and reinnervation.

We compared reinnervation of target organs after sciatic nerve section leaving gaps of 2, 4, 6, or 8 mm or gaps repaired with silicone tubes in different groups of mice. Functional reinnervation was assessed by noninvasive methods to determine recovery of sweating, nociceptive, and muscular functions in the hindpaw repeatedly during 3 months postoperation. The increase of gap length between nerve stumps delayed the beginning and reduced the degree of functional recovery achieved either with or without repair. When lesions were left unrepaired, functional reinnervation was only noticeable with a 2-mm gap and practically absent with longer gaps. With tube repair, reinnervation started earlier and achieved higher values than in the corresponding unrepaired groups. Tubulization was most effective with 4-mm gaps and comparatively less with shorter and longer gaps. With 4-mm gaps, recovery was higher when the silicone tube had a cross-sectional area 2.5 times that of the sciatic nerve than with narrower or wider tubes and when the wall was the thinnest available. In all cases muscle reinnervation showed a lower progression than sweating and nociceptive recovery.

Action Potentials↗
PubMed1995

The effect of aging on efferent nerve fibers regeneration in mice.

This study evaluates the influence of aging on nerve regeneration and reinnervation of target organs in mice aged 2, 6, 9, 12, 18 and 24 months. In animals of each age group the sciatic nerve was subjected to crush, section or section and suture. Reinnervation of plantar muscles and sweat glands (SG) was evaluated over three months after operation by functional methods. Reappearance of SG secretion and motor responses occurred slightly earlier in young than older mice. The degree of motor and sudomotor reinnervation, with respect to preoperative control values, was also significantly higher in young than old animals. The differences were more pronounced after 12 months of age. The degree of recovery progressively decreased with the severity of the lesion, differences being more marked in older mice. Neurorraphy improved recovery, comparatively more in older than in young mice. These results indicate that, after injuries of peripheral nerves, axonal regeneration and reinnervation are maintained throughout life, but tend to be more delayed and slightly less effective with aging.

Aging↗
PubMed1995

Functional sudomotor responses to cholinergic agonists and antagonists in the mouse.

This study evaluates the functional activity of the mouse sweat glands in response to cholinergic agonists and antagonists using the silicone imprint technique. In intact mice the response to acetylcholine, methacholine and pilocarpine did not differ significantly from control saline injection, indicating that immobilization induces high levels of sweating, masking the effects of cholinergic stimulation. Plantar emotional sweating was completely abolished by local anesthesia at the ankle. Under these conditions, administration of acetylcholine only provoked detectable sweating when injected locally into the sole skin. Methacholine activated an increasing number of sweat glands in a dose-dependent manner between 0.5 and 10 mg/kg; the response was maximal after 5-10 min of administration and decreased subsequently. With pilocarpine the maximum number of reactive sweat glands was observed at a dose of 2.5 mg/kg. The response was stable for 45 min with doses 2.5 and 5 mg/kg, but decreased exponentially with higher doses. The subtype of sweat gland muscarinic receptor was characterized by determining the inhibitory effect of different cholinergic antagonists on pilocarpine response. Atropine and 4-DAMP were equally potent inhibitors, showing a dose-related effect from 0.05 mg/kg. Pirenzepine only showed inhibitory effects with doses 10-times higher, whereas gallamine and hexamethonium did not induce inhibition at any of the doses tested. These findings suggest that the mouse eccrine sweat gland muscarinic receptors are predominantly M3.

Animals↗
PubMed1995

Innervation of cutaneous structures in the mouse hind paw: a confocal microscopy immunohistochemical study.

The normal innervation of structures in mouse foot pads was investigated with immunohistochemistry and confocal microscopy. Nerves were visualized by incubating Zamboni fixed, thick, frozen sections with antibodies to protein gene product 9.5 (PGP 9.5), vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, and protein zero. The antibodies were localized using cyanine 3.18 labeled anti-rabbit gamma globulin. PGP 9.5 immunolocalization showed dense nerve bundles at the base of the foot pad with branches to larger blood vessels, sweat glands and epidermis. Sweat gland tubules were surrounded by numerous sudomotor axons; single fibers accompanied the sweat duct toward the skin's surface. Nerve bundles containing myelinated and unmyelinated axons ran through and around the centrally located sweat gland cluster to end in free nerve endings and Meissner's-like corpuscles at the apex of the foot pad. Other bundles running parallel to the epidermis gave arcuate branches that supplied epidermis on the sides of the pads with a rich nerve network, principally with free nerve endings that often reached the most superficial cell layers of epidermis. Calcitonin gene-related peptide-immunoreactive (-ir) nerves were distributed to dermis and epidermis in lower density than PGP 9.5-ir fibers. Substance P-ir fibers were less numerous; most terminated as free endings in deeper layers of epidermis. Vasoactive intestinal peptide-ir nerves almost exclusively innervated sweat glands, ducts and blood vessels, but not epidermis. The mouse hind paw has potential to serve as a model system for investigations of functional and morphological changes that affect peripheral and autonomic nerves under diverse experimental conditions.

Animals↗
PubMed1994

Effects of dizocilpine on autotomy behavior after nerve section in mice.

The effects of acute administration of dizocilpine (MK-801) at different perioperative times on autotomy behavior after sciatic and saphenous nerve transection were studied in the mouse. Control mice developed a severe self-mutilating behavior starting 1-3 days postoperation and reaching a maximum by 11 days. Mice injected with a single dose of dizocilpine (0.4 mg/kg i.p.) before operation, the 1st or 3rd postoperative day autotomized significantly less than controls. An 1-wk treatment with the same dose once a day did not show further benefit. A single administration of dizocilpine the 5th day after surgery slightly halted further progression of autotomy. Dizocilpine did not have any deleterious effect on normal peripheral nerve function. These results suggest that NMDA receptor blockade prevents development of hyperalgesia and neuropathic pain after peripheral nerve injuries but only when it is administered before or during the first 3 days after injury.

Animals↗
PubMed1994

Comparison of regenerative and reinnervating capabilities of different functional types of nerve fibers.

Functional reinnervation of sweat glands (SGs), skin, and muscle in the mouse paw after sciatic nerve lesions was evaluated to allow comparisons of the regeneration efficiency of different functional types of nerve fibers. In four groups of mice the sciatic nerve was crushed, sectioned, and left unrepaired or repaired by suture or tubulization. Reappearance of SG secretion and pinprick responses occurred slightly earlier than recordings of compound muscle and nerve action potentials in all groups. The degree of reinnervation, with respect to preoperative control values, of SGs and skin nociceptors was higher than the amplitude of the action potentials, mainly when the nerve injury was severe. The chances for recovery progressively decreased with the severity of the lesion, affecting the larger nerve fibers most. These results indicate that, after injuries of peripheral nerves, all types of nerve fibers are able to regenerate in the mouse, although small size fibers (sudomotor and nociceptive) allow for a higher degree of functional recovery than large myelinated fibers (skeletomotor and sensory).

Animals↗
PubMed1993

Abnormalities of sympathetic sudomotor function in experimental acrylamide neuropathy.

The possible involvement of sympathetic sudomotor function by acrylamide intoxication was investigated in the mouse, and compared with nerve conduction studies and global motor tests. Acrylamide (40 mg/kg, 3 days per week, 8 weeks) was given per os to a group of mice (A1). Their motor ability to stand on the rotarod was impaired from day 11, reaching a minimum between 46 and 60 days. The number of pilocarpine reactive sweat glands (SG), evaluated by the silicone mold technique, was similar to controls at 40 days and slightly decreased at 54 days. Another group of mice (A2), given acrylamide at a higher dose (50 mg/kg, 5 days per week, 5 weeks), showed abnormalities on the rotarod by 11 days, a progressive decrease of muscle action potential (CMAP) amplitude, and significantly decreased number of reactive SG from 15 days, with respect to controls. Comparatively, sudomotor dysfunction was milder and appeared later in time than alphamotor involvement, being noticeable only after severe poisoning. The decrease in SG response is attributable to damage by acrylamide intoxication of postganglionic sudomotor nerve fibers, which are unmyelinated sympathetic efferents.

Acrylamides↗
PubMedDate not supplied

Functional changes of the peripheral nervous system with aging in the mouse.

The influence of aging on peripheral nerve and target organ function was investigated in six groups of mice aged 2, 6, 9, 12, 18, and 24 months. Sudomotor, motor, and sensory functions mediated by the sciatic nerve were evaluated by silicone imprints, electrophysiological recordings and pinprick test from the distal hindpaw. Nerve conduction was also studied in the caudal nerves. The results showed that the number of sweat glands reactive to pilocarpine does not change significantly with aging, but the size of the sweat droplets is smaller in aged mice than in young mice. The amplitude of muscle and nerve action potentials evoked by stimulation of sciatic and caudal nerves decreased progressively from 2 to 24 months, while the latencies decreased from 2 to 6 months, remained unchanged until 12 months and increased thereafter. All the animals of the six groups studied showed positive, indistinguishable responses to pinprick. These results indicate that neurophysiological responses mediated by large diameter nerve fibers deteriorated with age, while those dependent of small fibers were preserved.

Aging↗
PubMedDate not supplied

[Methodological considerations concerning peripheral nerve morphometry].

Morphometric studies of the peripheral nerve often present widely varying results which, in part at least, may be attributed to the different methodologies used. Two questions may be of importance with regard to the reliability of such results: the preselection of fibres according to their morphology and the method used in quantifying observations. In this work a morphological study was carried out on the myelinated fibres of the sciatic nerve of a rat in order to evaluate fibre selection criteria. A morphometric analysis was also performed using manual measurements, image digitalisation and surveying, and automatic image analysis. It was shown that morphological variability of transverse section fibres is considerable and that, really, the proportion of circular fibres with homogeneous compact myelin is only 50 to 70%, from which we can conclude that the selection of fibres carried out in some studies wishing to eliminate abnormal fibres is somewhat exaggerated. By analysing the fibres using various methods significant differences appear, some due to the fact that distinct methods may be used to calculate the same parameters in a different way. The most reliable parameters would appear to be those which do not depend on the shape of the fibres and those which automatic or semiautomatic methods can calculate directly such as areas and perimeters. In any case quantifying methods seem hardly discriminatory and the differences between methods disappear if analyses are carried out using random samples. Preselection of fibres appears unnecessary in this context as in no case are the results altered. Finally we suggest finishing quantitative analyses with qualitative studies which would permit getting more information especially useful in cases of ageing, regeneration or pathological studies.

Aging↗
PubMedDate not supplied

[Degeneration and regeneration of the peripheral nervous system with aging].

Clinical and experimental studies have shown that with aging there appear neurological changes which affect both the Central Nervous System (CNS) as well as the Peripheral Nervous System (PNS), bringing about a series of cognitive, sensory and physical disabilities in older people. Nerve lesions also cause disability. The basic mechanisms which begin with lesioned neurons have proved an interesting field of study for many neuroscientists since as far back as the mid-nineteenth century. However the influence of age on these postlesion neuronal processes has not aroused the same level of interest even though many authors have, out of curiosity, published reports of changes which take place in regenerative neurons as a result of age. The progressive increase in the aged population in industrialised nations warrants a detailed study into the influence of age on such neuronal processes. The PNS, due to its accessibility and greater regenerative potential vis-à-vis the CNS, may be a good model for this purpose. From results obtained by both other authors and ourselves it is clear that aging causes a decline in the regenerative abilities of peripheral nerve fibres. Functional recovery is not only slowed down but also decreases with age. The number of regenerative axons and their capacity for end sprouting, together with the biosynthesis and transport of new materials in the regenerative neurons, as well as the proliferation and synthesis of trophic factors by Schwann cells also decay. All of this leads to the fact that the regenerative capacity of nerve fibres is lesser with age, and that functional disabilities after a lesion are greater in older than in younger people.

Aging↗