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Biomedical subjects

A Nicotra

Publications and source records attributed to A Nicotra.

At least 19 recordsLinked to original sources
PubMed2006

Skin vasomotor reflex responses in two contrasting groups of autonomic failure: multiple system atrophy and pure autonomic failure.

BACKGROUND & AIM: A variety of stimuli such as deep inspiration, isometric exercise and mental arithmetic, result in a transient vasoconstriction,mediated by sympathetic efferent nerves, in the skin of the fingers and toes of healthy controls (Skin Vasomotor Reflex: SkVR). Multiple system atrophy (MSA) and pure autonomic failure (PAF) provide contrasting models of autonomic failure. In MSA the lesion is central and preganglionic, whilst in PAF the lesion site is peripheral and postganglionic. We evaluated the SkVR in response to various stimuli in MSA and PAF, to determine differences in skin vasomotor involvement between these two patient groups. METHODS: 25 subjects (10 MSA, 7 PAF, 8 healthy controls) were studied. Baseline recordings of skin blood flow were obtained with a laser Doppler probe on the left index finger pulp and forearm. The subject then underwent a variety of stimuli with rest periods in between to reestablish baseline SkBF. These stimuli were: single deep inspiration (inspiratory gasp); mental arithmetic; bilateral leg elevation and cutaneous cold. RESULTS: Healthy control subjects demonstrated marked SkVRs on the finger pulp to each of the stimuli of a magnitude similar to those seen in previous studies, but no SkVRs on the forearm. In MSA SkVRs to inspiratory gasp on the finger pulp were reduced relative to controls. In PAF SkVRs were reduced relative to controls or MSA. The magnitude of SkVR response to gasp and cutaneous cold in PAF was significantly less than in healthy controls. In addition, the magnitude of the response in PAF was significantly less than in MSA for inspiratory gasp. CONCLUSIONS: PAF showed a decreased SkVR response to all 4 stimuli, the response being significantly less than controls (for inspiratory gasp and cutaneous cold) or MSA (cutaneous cold inspiratory gasp). The decreased responses in PAF may reflect the extensive postganglionic sympathetic denervation seen in this group. The measurement of SkVR may therefore provide a non-invasive aid to the differentiation of MSA and PAF.

Age Factors↗
PubMed2006

Thermal perception thresholds: assessing the level of human spinal cord injury.

STUDY DESIGN: Controlled, cross-sectional, observational. OBJECTIVES: To investigate whether quantitative sensory testing (QST) is able to reveal subclinical deficits at the neurological level of lesion in subjects with chronic spinal cord injury (SCI). SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital and Imperial College London, UK. METHODS: QST and clinical assessments were carried out on 18 subjects with complete SCI (American Spinal Injury Association (ASIA) grade A) and 10 subjects with incomplete SCI (ASIA grades B, C or D). A total of 10 healthy subjects acted as controls. RESULTS: At the level of lesion perceptual thresholds to monofilaments, cold pain and heat pain were similar to values in control subjects but cool and warm thresholds were significantly raised. A correlation between cool and warm thresholds was observed at the level of lesion in complete SCI and between heat and cold pain thresholds at the level of lesion in complete SCI, incomplete SCI and in control subjects. In the zone of partial preservation in complete SCI and below the level of lesion in incomplete SCI, thresholds for all modalities were all different compared to controls. CONCLUSION: QST reveals impaired thermal sensation in dermatomes clinically defined as normal with ASIA standards. Quantitative thermal testing therefore permits a discriminating assessment of preserved sensation and subclinical deficit and has the potential to improve upon the clinical detection of natural recovery or changes in level of injury following interventions designed to repair SCI.

Adult↗
PubMed2006

Heat-provoked skin vasodilatation in innervated and denervated trunk dermatomes in human spinal cord injury.

STUDY DESIGN: Cross-sectional, observational, controlled study. OBJECTIVE: High spinal cord injury (SCI) results in disruption of sympathetic vasomotor control. Vasodilatation as a response to local heating is a biphasic mechanism: the first phase (neurogenic) is mediated by the axon-reflex and is modulated by activity of sympathetic nerves. Our objective was to determine whether the response to heat provocation in trunk dermatomes may provide a measure of vasomotor sympathetic function in SCI. SETTING: National Spinal Injuries Centre, Stoke Mandeville Hospital, Buckinghamshire, UK; Autonomic Unit, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Neurovascular Medicine Unit, Imperial College London at St Mary's Hospital, UK. SUBJECTS: A total of 30 subjects were studied; 18 had chronic complete SCI (level C6-T11) and 12 were healthy controls. METHODS: Recordings of skin blood flow (SkBF) were obtained with thermostatic laser Doppler probes placed in the upper trunk (at C4) and lower trunk (T10 or T12) dermatomes. RESULTS: SkBF at baseline (SkBF(bas)) and SkBF at the first peak of vasodilatation (SkBF(max)) showed no significant differences between SCI and controls either in upper or lower trunk dermatomes. However, the ratio of SkBF(max)/SkBF(bas) was significantly different in lower trunk dermatomes in SCI at C6-T5 level (7.5+/-3.5 PU) compared to SCI at T6-T11 level (3.5+/-1.5 PU) (P < 0.01). CONCLUSION: Measurement of SkBF in response to local heating may provide a safe, noninvasive method to assess integrity of sympathetic spinal pathways to the local vasculature. This may aid the classification of the SCI lesions, as the autonomic component currently is not included in the accepted American Spinal Injury Association scoring.

Adult↗
PubMed2005

Blood-brain barrier-specific properties of a human adult brain endothelial cell line.

Establishment of a human model of the blood-brain barrier has proven to be a difficult goal. To accomplish this, normal human brain endothelial cells were transduced by lentiviral vectors incorporating human telomerase or SV40 T antigen. Among the many stable immortalized clones obtained by sequential limiting dilution cloning of the transduced cells, one was selected for expression of normal endothelial markers, including CD31, VE cadherin, and von Willebrand factor. This cell line, termed hCMEC/D3, showed a stable normal karyotype, maintained contact-inhibited monolayers in tissue culture, exhibited robust proliferation in response to endothelial growth factors, and formed capillary tubes in matrix but no colonies in soft agar. hCMEC/D3 cells expressed telomerase and grew indefinitely without phenotypic dedifferentiation. These cells expressed chemokine receptors, up-regulated adhesion molecules in response to inflammatory cytokines, and demonstrated blood-brain barrier characteristics, including tight junctional proteins and the capacity to actively exclude drugs. hCMEC/D3 are excellent candidates for studies of blood-brain barrier function, the responses of brain endothelium to inflammatory and infectious stimuli, and the interaction of brain endothelium with lymphocytes or tumor cells. Thus, hCMEC/D3 represents the first stable, fully characterized, well-differentiated human brain endothelial cell line and should serve as a widely usable research tool.

Agar↗
PubMed2004

Towards improved clinical and physiological assessments of recovery in spinal cord injury: a clinical initiative.

Clinical practice and scientific research may soon lead to treatments designed to repair spinal cord injury. Repair is likely to be partial in the first trials, extending only one or two segments below the original injury. Furthermore, treatments that are becoming available are likely to be applied to the thoracic spinal cord to minimise loss of function resulting from damage to surviving connections. These provisos have prompted research into the improvement of clinical and physiological tests designed (1) to determine the level and density of a spinal cord injury, (2) to provide reliable monitoring of recovery over one or two spinal cord segments, and (3) to provide indices of function provided by thoracic spinal root innervation, presently largely ignored in assessment of spinal cord injury. This article reviews progress of the Clinical Initiative, sponsored by the International Spinal Research Trust, to advance the clinical and physiological tests of sensory, motor and autonomic function needed to achieve these aims.

Animals↗
PubMed2004

Skin vasodilator response to local heating in human chronic spinal cord injury.

Local heating evokes an increase in skin blood flow (SkBF), which consists of an initial peak (axon-reflex mediated) followed by a brief nadir and a secondary rise to a plateau. The aim of this study was to investigate whether heat provoked vasodilatation detects sympathetic vasomotor dysfunction and completeness of injury in patients with spinal cord injury (SCI). Twelve (seven complete, and five incomplete; level C4-L4) SCI patients, and nine healthy subjects as controls were studied. Thermostatic laser Doppler probes, which heat the skin locally, were placed on the dorsum of the hand and foot. SkBF was measured by laser Doppler flowmetry at baseline and at the first peak of vasodilatation (SkBF(max)). On the hand, SkBF at baseline and SkBF(max) were similar between the three groups. On the foot, SkBF at baseline was similar between the three groups but SkBF(max) was significantly diminished in complete SCI patients compared with controls (P < 0.01). In conclusion, heat provoked axon-reflex vasodilatation was diminished in the foot, below the level of lesion, in complete SCI. This test, that evaluates localized sympathetic vasomotor dysfunction, may be a useful non-invasive technique to detect completeness of autonomic disruption after SCI.

Adult↗
PubMed2000

Cell death induced by MPTP, a substrate for monoamine oxidase B.

MPTP is known to cause PD symptoms in primates and in rodents. In order to exert its neurotoxicity MPTP must be converted by monoamine oxidase B into MPP(+) which is the true toxic agent. MPP(+) is taken up by the dopaminergic neurons of the substantia nigra in which it induces cell death. The present work reviews and discusses papers in which specific methods were used to determine whether cell death induced by MPTP/MPP(+) should be considered as apoptosis or necrosis. These two cell death modes may be distinguished using morphological and biochemical criteria. The effect of MPTP/MPP(+) was studied in vitro and in vivo. The results show that no univocal answer is possible. The most widespread interpretation is that MPTP/MPP(+) causes apoptosis when its neurotoxic effect is only sligh and necrosis when it is stronger. Similar considerations may be made also concerning the type of cell death occurring in the dopaminergic neurons in the substantia nigra of PD patients.

Animals↗
PubMed2000

Phenotypic differences between African and white patients with motor neuron disease: a case-control study.

There is increasing evidence that race may affect the phenotype in some neurodegenerative diseases. To investigate this in motor neuron disease a retrospective case-control study has been carried out on 15 negroid African and 45 white patients with the disease seen over 8 years. Each African was compared with three age and sex matched white patients with motor neuron disease. There were no statistically significant differences in age of onset or the mean duration of disease in the two groups. The chance of presenting with the "flail arm" variant of motor neuron disease was four times as high in the African group than the white group (odds ratio 4.33, p=0. 05, 95% confidence interval 0.99-18.92). Although no overall differences in survival were seen between the two groups, in those with the flail arm variant, four out of the six African patients had died whereas all six white arm patients were alive at the censoring date of 1 January 1999 (median follow up 38.5 months). It is concluded that race may influence the phenotype and progression of motor neuron disease.

Africa↗
PubMed1996

Propranolol induces polyspermy during sea urchin fertilization.

Propranolol, a beta-adrenergic receptor blocker, is found to induce polyspermy in sea urchin eggs. Unfertilized sea urchin eggs treated for 10 min with 50 microM of propranolol, and then inseminated, become polyspermic and show a fertilization envelope which is barely visible to the light microscope. Examination of treated eggs by transmission and scanning electron microscopy shows that the drug does not alter the cortex of the unfertilized egg. However, after insemination an incomplete cortical reaction occurs. This might well account for both polyspermy and the defective elevation of the fertilization envelope. Since the effects of the drug are reversed by simultaneous treatment with adrenalin, perhaps propranolol interferes with the monoaminergic system that has been proposed to be active. The involvement of the monoaminergic system in the fertilization process is present in the sea urchin egg.

Animals↗
PubMed1990

Propranolol, a beta-adrenergic receptor blocker, affects microfilament organization, but not microtubules, during the first division in sea urchin eggs.

Propranolol, a beta-adrenergic receptor blocker, blocks the formation of the cleavage furrow, while karyokinesis is unaffected during first division in the sea urchins Paracentrotus lividus or Lytechinus pictus. This effect is reversed by adrenalin, indicating that it is mediated by an adrenergic mechanism. The staining of F-actin microfilaments by rhodamine phalloidin in eggs in which the cleavage is blocked by the drug has revealed that propranolol affects both the distribution and the organization of actin microfilaments. A low-voltage scanning electron microscopy (LVSEM) study of microvilli in these eggs shows an extensive rearrangement of the egg surface. Anti-tubulin immunofluorescence microscopy of eggs treated with propranolol shows that they form normal mitotic asters. This indicates that while cleavage is affected, mitotic spindle formation is not. These results suggest that neurotransmitter monoamines known to be present in the sea urchin egg might be involved in the reorganization of the actin cytoskeleton underlying the formation of the cleavage furrow.

Actin Cytoskeleton↗
PubMed1990

Monoamine oxidase activity in embryos of pike (Esox lucius).

1. Mitochondrial MAO specific activity was measured in eggs and early embryos of the teleostean fish Esox lucius using tryptamine, 5-hydroxytryptamine (5-HT) and phenylethylamine (PEA) as substrates. 2. Tryptamine is the most readily deaminated substrate in mitochondria isolated from unfertilized eggs and embryos at the stages of cleavage, blastula and gastrula. 3. Monoamine oxidase activity gradually decreases during development and at the gastrula stage it is respectively 80% (tryptamine), 70% (5-HT) and 50% (PEA) of that found in the egg using the corresponding substrate. 4. The inhibition of egg MAO activity by clorgyline and deprenyl measured in E. lucius eggs using tryptamine as substrate, indicates the presence of a single form of MAO not corresponding to the MAO A and MAO B described in terrestrial vertebrates.

Animals↗
PubMed1989

Some characteristics of mitochondrial monoamine oxidase activity in eggs of carp (Cyprinus carpio) and rainbow trout (Salmo gairdneri).

1. Monoamine oxidase (MAO) activity towards tryptamine, 5-hydroxytryptamine (5-HT) and phenylethylamine (PEA) has been measured in mitochondria isolated from carp and trout eggs. 2. In carp eggs all the tested substrates are metabolized and the highest affinity is found with tryptamine. In trout eggs a consistent level of MAO activity is obtained using tryptamine. 3. The inhibition dose-response curves of clorgyline and deprenyl indicate that both in carp and trout eggs there is only one form of mitochondrial MAO, distinct from MAO A and B which have been described in vertebrate tissues. 4. Both in carp and trout egg mitochondria a semicarbazide-sensitive amine oxidase is not involved in the deamination of the used substrates. 5. MAO found in carp and trout eggs might be involved in metabolism of some neurotransmitter monoamines during early developmental stages.

Animals↗
PubMed1988

Changes in monoamine oxidase activity by mitochondria isolated from late embryos of Bufo bufo.

1. Monoamine oxidase activity has been assayed in mitochondria isolated from post-neural embryos (stages 14-25) of Bufo bufo, using 5-HT and PEA as substrates. 2. Mitochondria isolated from stages 19 to 25 show an increasing ability in deaminating monoamines, PEA being metabolized at a higher level with respect to 5-HT. 3. At all the examined stages 5-HT is metabolized by an enzyme corresponding to MAO A, while PEA, from stage 19, is largely deaminated by a semicarbazide-sensitive amine oxidase (SSAO). 4. The effect of Triton X-100 on MAO A activity appears remarkably different in mitochondria isolated from embryos at stages 14 and 25 respectively.

Animals↗
PubMed1988

Monoamine oxidase and semicarbazide sensitive amine oxidase activities in toad liver mitochondria.

1. The deamination of 5-HT and PEA has been assayed by a radiochemical method in mitochondria isolated from toad liver. 2. Time courses of 5-HT and PEA deamination indicate that when PEA is used as the substrate, higher specific activities are obtained. 3. 5-HT is deaminated by MAO A and partially by a SSAO-like enzyme. 4. PEA is deaminated exclusively by SSAO and, MAO B activity, at least under the adopted experimental conditions, is not detectable.

Animals↗
PubMed1985

Mitochondrial monoamine oxidase activity during preneural developmental stages of Bufo bufo.

Monoamine oxidase specific activities against PEA and 5-HT have been measured in mitochondria isolated from early embryos of Bufo bufo. During the early development up to the neural fold stage, MAO activity undergoes a continuous decrease that is more evident when PEA is used as the substrate. The inhibition patterns of deprenyl and clorgyline demonstrate that, at the neural fold stage, both type A and B MAO are present. Both in eggs and embryos MAO type A activity appears slightly more sensitive to the inhibitory effect of various concentrations (0.1-2 M) of the denaturing agent urea.

Animals↗
PubMed1984

Occurrence of type A and type B monoamine oxidase activities in toad egg mitochondria.

Monoamine oxidase activity has been assayed radiochemically in mitochondria from Bufo bufo eggs. Time courses of MAO activity towards PEA and 5-HT indicate that when PEA is used as a substrate higher specific activities are obtained. The inhibition patterns by clorgyline and deprenyl demonstrate that both type A and type B MAO are present. Type A activity is more sensitive than type B to the inhibitory effect of Triton X-100. Low concentrations of 2-mercaptoethanol cause a slight stimulation of type A and B activities. Increasing concentrations result in a decrease of activity.

Animals↗