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Biomedical subjects

X Navarro

Publications and source records attributed to X Navarro.

At least 55 records · Page 3Linked to original sources

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↗

Peripheral nerve repair: role of agarose matrix density on functional recovery.

This study presents quantitative data on the functional reinnervation of sweat glands, muscle and skin in the mouse paw after resection of the sciatic nerve and repair by entubulation with silicone tubes prefilled with agarose gels of different concentrations. The rate and the degree of functional recovery of animals with chambers filled with 0.5% agarose gels were slightly higher than with 1% agarose, and significantly higher than with 2% agarose. All these three groups recovered significantly better than a fourth group with an unrepaired resection. We conclude that peripheral nerves can regenerate through agarose gels in vvio and reinnervate distal target organs, but the concentration and the density of the exogenous intratubular matrix are important factors in determining the success of nerve regeneration and reinnervation.

Animals↗

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↗

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↗

Autonomic neuropathy in chronic alcoholism: evaluation of cardiovascular, pupillary and sympathetic skin responses.

Autonomic nerve function was evaluated in 30 alcoholics and 30 healthy subjects by means of cardiovascular function tests, pupil cycle time (PCT), and sympathetic skin responses (SSR). Nutritional status was assessed by anthropometric parameters. Autonomic cardiovascular dysfunction was classified as early involvement in 5 patients, definite in 8, severe in 6 and atypical in 3. PCT was abnormal in 17 alcoholics. The duration of PCT became progressively longer as the severity of cardiovascular involvement increased. SSR was absent in 4 alcoholics in the palm and in 16 in the sole. These findings indicate that sympathetic and parasympathetic mediated functions are abnormal in chronic alcoholics with a similar frequency, involving different sites of the autonomic nervous system under variable patterns. Significant correlations between nutritional status and autonomic neuropathy were found.

Adult↗

Neuropathy profile of diabetic patients in a pancreas transplantation program.

We describe the results of extensive neurologic evaluation of 290 patients with insulin-dependent diabetes mellitus who came to our institution as potential recipients of a pancreas transplant. Large nerve fibers were evaluated by motor and sensory nerve conduction, small sensory fibers by thermal sensation thresholds, vagal and vasomotor functions by cardiovascular reflexes, and sympathetic sudomotor fibers by silicone imprints and evaporimetry. A scored anamnesis revealed symptoms of neuropathy in 86% of patients; 94% had an abnormal neurologic examination. The most frequently abnormal measurements of motor conduction were the amplitude of the extensor digitorum brevis muscle action potential to peroneal nerve stimulation and the conduction velocity of peroneal and tibial nerves in more than 80% of patients. Sensory nerve action potentials were abnormal in 76% and the distal latency of the sural nerve in 91%. Heart rate variability with deep breathing and during a Valsalva's maneuver was abnormal in 90% and 88%. Sudomotor function was reduced in 59% on the foot. Thermal sensitivity limen was above normal limits in 95% in the foot and 77% in the hand. Composite indexes of the degree of abnormality found for each type of function tested were correlated one with another, but were not predictive of results for any other test. The neuropathy of most patients was symmetric, involving to a similar degree motor, sensory, and autonomic nerves. Thus, diabetic neuropathy is very common and severe among patients who decide to be candidates for pancreas transplantation.

Adult↗

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↗

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↗

Comparison of sympathetic sudomotor and skin responses in alcoholic neuropathy.

We evaluated sympathetic sudomotor and parasympathetic vagal function in 30 chronic alcoholic patients and 28 control subjects by means of silicone imprints, sympathetic skin responses (SSR), and cardiorespiratory reflex tests. Mean values from alcoholic patients were significantly lower than those from control subjects for all tests. The number of secreting sweat glands (SGN) was below normal in the foot of 18 patients, and in the hand of 7 patients; 16 patients had absent SSR on the sole, and 4 on the palm. Only two patients had both test results abnormal on the hand and 10 on the foot. The SGN did not correlate with the amplitude of the SSR in the subjects studied. There was no clear correlation of abnormalities found in cardiorespiratory tests and sympathetic tests. Abnormalities in sensory nerve conduction were associated with absent SSR, but not with decreased SGN. The silicone mold technique is a more specific test to detect abnormalities in sympathetic efferent fibers, as SSR may be influenced by sensory afferent fiber involvement.

Adult↗

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↗

Influence of posture on cardiorespiratory reflexes in normal subjects and patients with diabetes mellitus.

This study was designed to assess the effect of patient posture, either sitting or supine, on the results and diagnostic yield of tests of cardiorespiratory reflexes on 25 normal subject controls and 128 patients with diabetes mellitus. The heart rate changes during slow breathing at 6 per minute (delta R6) and during a Valsalva manoeuvre (highest heart rate during manoeuvre divided by lowest heart rate within 30 s after manoeuvre; Valsalva ratio) were measured from the electrocardiographic signal and tachometry. In control subjects, heart rate changes during slow breathing averaged 25.0 when sitting and 21.3 when supine (p < 0.01); Valsalva ratio averaged 1.90 and 1.83 (p > 0.2) respectively. In diabetic patients, mean values for heart rate changes during slow breathing were 6.1 and 5.1, and mean values for Valsalva ratio were 1.23 and 1.28 in sitting and supine postures respectively. According to our normal limits, heart rate changes during slow breathing was below normal in 109 patients tested when sitting and in 113 tested when supine, and Valsalva ratio was abnormal in 103 and 95 respectively. These results indicate that subject posture is an important variable of cardio-respiratory reflex testing, and should be standardized to allow comparisons of individual results.

Adult↗

The effects of autologous nerve transplants on motor and sudomotor reinnervation by regenerative axons.

The functional reinnervation rate of sweat glands (SGs) and muscle in the mouse paw were compared following resection of a 4 mm segment of sciatic nerve. Repair was by graft of the same segment with epineural sutures or by suturing the proximal and distal stumps to a teflon tube that contained saline alone or saline plus the unattached nerve segment. Pilocarpine activated SGs first reappeared at 23 days postoperation in mice with a direct graft, at 29 days in mice with a nerve transplant in the tube, and at 32 days in mice with an empty tube. The number of reinnervated SGs increased progressively in number to a maximum of about 65% of the control counts by 60, 60 and 67 days, respectively. Compound muscle action potentials evoked by sciatic nerve stimulation were first recorded from the interossei muscles at 24, 27 and 31 days postoperation in the same groups of mice. The action potential amplitude increased to average values of about 2 mV by 58, 62 and 69 days. These results indicate that a direct nerve graft allows faster and higher functional recovery than tubulation repair, and that a nerve transplant slightly accelerates the reinnervation rate, probably due to the presence of nerve trophic products inside the tube. Unmyelinated and myelinated axons regenerated at equal rates.

Action Potentials↗

Quantitation of the alternate movement rate in normal and diabetic subjects.

Functional abnormalities of alternate movement rate (AMR) of finger and foot tapping were quantitated in 162 patients with diabetic neuropathy and 30 control subjects using a simple electronic device. The quantitative AMR (QAMR) averaged 29.5 +/- 3.0 for finger tapping and 20.4 +/- 3.7 for foot tapping in controls, and 27.5 +/- 4.8 (P less than 0.05) and 17.0 +/- 5.6 (P less than 0.005) for finger and foot, respectively, in diabetic patients. Fifty-one patients had abnormal QAMR in the finger and 79 in the foot. The QAMR values correlated with the results of nerve conduction studies of patients. Testing for abnormalities of AMR is a useful addition to the testing of dysfunction secondary to diabetic neuropathy. It provides quantitation of a common, subject-initiated, functional task more accurately than possible by clinical observation.

Adult↗

Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation.

Cardiorespiratory reflexes were studied during slow breathing and a Valsalva maneuver in 232 Type 1 (insulin-dependent) diabetic subjects. At 1 to 7 years follow-up, death occurred in 23.4% of 175 patients with abnormal reflexes and in 3.5% of 57 patients with normal reflexes. The mortality rates of diabetic subjects with abnormal reflexes were 17% at 2.5 years, 33% at 5 years and 40% at 7 years, significantly higher than for patients with normal reflexes (4.6%, 4.6% and 13.8%). Among patients with abnormal reflexes, patients with a functioning pancreas transplantation had better survival rates than patients with a failed transplantation, and in long-term follow-up better than patients without transplantation. A functioning transplantation prevented the progressive decline of cardiorespiratory reflex function that occurred over time in control patients.

Adult↗

Cardiovascular responses to tilting in healthy and diabetic subjects.

Cardiovascular responses to tilting from supine to upright and back to supine were investigated by measuring heart rate (HR) and blood pressure (BP) continuously by non-invasive methods. Subjects were 20 healthy controls, 17 diabetic patients (DN) with normal test results for parasympathetic cardiac function and 21 diabetics (DA) with abnormal results. In control subjects, tilting up and tilting back maneuvers induced opposite changes in HR, systolic (SBP) and diastolic BP (DBP). The most obvious responses appeared during the first 30 sec after either maneuver. The best measurements to detect sympathetic vasoconstrictor abnormalities during tilting up were derived from the recovery curve that followed the immediate fall in SBP, abnormal in 6 DN and 14 DA patients, and from the increase in DBP after the maneuver, abnormal in 7 and 16, respectively. Tilting back induced comparatively larger cardiovascular responses. The SBP remained stable after 10 sec in the controls, but increased above normal limits in 7 DN and 20 DA patients. The DBP fell during the first 10 sec in controls, but not in 4 DN and 17 DA patients. Continuous monitoring of BP during tilting is a more sensitive test of autonomic function than classical BP measurements made at a few selected intervals. The results challenge the view that parasympathetic dysfunction precedes and occurs more frequently than sympathetic dysfunction.

Adult↗

Effects of laminin on functional reinnervation of target organs by regenerating axons.

Reinnervation of sweat glands, skeletal muscle and skin was studied in the mouse paw after section of the sciatic nerve and repair by entubulation with collagen conduits, with and without a coating of laminin. After operation, sweat glands activated by pilocarpine reappeared at 32 days and increased in number to 67% of control counts. Muscle action potentials (during sciatic nerve stimulation) were recorded from the interosseus muscle at 39 days. The potential amplitudes increased to 30% of controls. The first withdrawal response from pin prick to the paw was observed at about 34 days, the response score increasing to 66% of control. There were no significant differences at any test interval between the control group and the group with laminin added.

Animals↗