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Biomedical subjects

F Fantini

Publications and source records attributed to F Fantini.

At least 91 records · Page 5Linked to original sources

Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes.

An involvement of neurogenic components in the pathogenesis of psoriatic lesions has been suggested and neuropeptides are thought to play a modulatory role in cutaneous inflammation. In this study, we evaluated the immunoreactivity of the neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the skin of patients with chronic plaque psoriasis, by immunohistochemistry and radioimmunoassay. No differences were observed, by immunohistochemistry, in the expression and localization of VIP and SP between psoriatic and normal skin. Using the radioimmunologic technique on whole skin homogenates, VIP levels were significantly increased in psoriatic lesions as compared to normal skin. By contrast, SP levels were significantly lower in lesional and non-lesional psoriatic skin than in normal skin. In addition, we examined the effect of VIP and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1 nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1 microM) stimulated the proliferation of keratinocytes in a dose-dependent manner, whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not only failed to stimulate keratinocyte growth, but also blocked the VIP-induced stimulation of these cells. The imbalance of cutaneous VIP and SP and their disparate effects on the proliferation of normal human keratinocytes in culture would suggest that these peptides are involved in the pathogenesis of psoriasis and may exert different modulatory activities in the mechanisms underlying the psoriatic lesion.

Cell Division↗

Expression of growth-associated protein 43 and nerve growth factor receptor in human skin: a comparative immunohistochemical investigation.

The growth-associated protein 43 (GAP43) is a neuronal membrane protein involved in axonal growth and regeneration as well as in the modulation of synaptic plasticity. It is present in sensory and sympathetic neurons, where it is consistently associated with the expression of nerve growth factor receptor (NGFr). We investigated, by means of immunohistochemistry, the presence and distribution of the GAP43-immunoreactivity (IR) and of the NGFr-IR in the adult normal human skin from various body regions. In adjacent sections, a comparison with the distribution of the neuronal markers protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) was performed. Our results indicate that in adult human skin 1) a GAP43-IR is morphologically present in epidermal and dermal nerve fibers; 2) a NGFr-IR is associated with neuronal as well as non-neuronal elements of cutaneous nerves; 3) the basal epidermal cell layer expresses a NGFr-IR, which is unevenly distributed according to the different body areas; and 4) there is suggestive evidence for a simultaneous expression of GAP43-, NGFr-, PGP 9.5-, SP-, and CGRP-IR in at least part of the cutaneous nerve fibers. The presence of GAP43-immunoreactive nerve fibers might be a marker of a continuous synaptic remodeling in adult skin, whereas the distribution of the NGFr-IR could be relevant for our understanding of the maintenance of the neuronal-target relationship(s).

Adult↗

Substance P levels are decreased in lesional skin of atopic dermatitis.

There is increasing evidence that neuropeptides (NP) such as substance P (SP) and vasoactive intestinal polypeptide (VIP) are involved in the pathogenesis of atopic dermatitis (AD). Vasoactive intestinal polypeptide levels were found to be significantly elevated in lesional skin of AD as compared to controls. We evaluated by radioimmunoassay the SP content in whole skin homogenates from chronic lichenified lesions of patients with AD. The levels of SP were significantly decreased in lesional skin from AD patients as compared to control skin (0.25 +/- 0.03 vs. 0.97 +/- 0.24 pmol/g tissue, p < 0.01). The diminished SP levels as opposed to increased VIP concentrations could be consistent with different roles of these NP as modulatory agents in the mechanisms associated with AD.

Adolescent↗

Vasoactive intestinal polypeptide and substance P in the pathogenesis of atopic dermatitis.

Neurogenic components are probably involved in the pathogenesis of atopic dermatitis (AD) and several neuropeptides have been implicated in the mechanisms underlying this disease. The aim of the present study was to evaluate by radio-immunoassay (RIA), the vasoactive intestinal polypeptide (VIP) and substance P (SP) content in whole-skin homogenates of AD lesions. RIA was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment VIP (22-28) and a polyclonal antiserum directed against SP. VIP levels were markedly increased in lesional AD skin (5.62 +/- 1.25 pmol/g tissue) vis-à-vis controls (0.43 +/- 0.08 pmol/g tissue), whereas SP levels were significantly lower in lesional skin (0.25 +/- 0.03 pmol/g tissue) than in normal skin (0.97 +/- 0.24 pmol/g tissue). The results confirm that VIP and SP are relevant to the pathogenesis of AD and their imbalance might reflect diverse roles of these NP in the modulation of AD lesion.

Adolescent↗

Cutaneous innervation in chronic renal failure patients. An immunohistochemical study.

Most chronic renal failure patients suffer from generalized pruritus. An involvement of cutaneous nerve terminals in the pathogenesis of uremic pruritus has been suggested. Skin specimens from 24 uremic patients and 10 healthy subjects were processed with an indirect immunofluorescence method to investigate the presence and distribution of a number of neuronal markers and neuropeptides. No difference was found between the two groups in the distribution pattern of the positive nerve fibres. However, a reduction in the total number of skin nerve terminals in the uremic patients was detected. No correlation could be found between the immunohistochemical findings and the clinical features. Our results suggest that the skin innervation is altered in most chronic renal failure patients, possibly as a consequence of neuropathy.

Adult↗

[Analysis of regional kinetics of the left ventricle by integration of morphologic data].

Regional left ventricular (LV) curvature analysis is a useful tool to assess the pathomorphological changes in LV shape which occur in different heart diseases. As LV shape changes follow regular trajectories, we used the curvature extrema and the normalized curvature variations as the features for identifying the movement of the borders during the cardiac cycle (curvature-motion method: CM). The regional curvature was calculated using a windowed Fourier series approximation of contours, in which the number of harmonics and filter-window were locally chosen in order to minimize the reconstruction errors and to maximize the smoothness of the curve. Analysis programs were tested on a series of ventricle-shaped contours, software generated. Left ventricular diastolic and systolic outlines obtained from RAO 30 degrees LV angiography in 24 patients with aortic insufficiency and in 16 subjects without heart disease were analyzed. Left ventricular curvature and regional wall motion were calculated in each subject. In respect to normal subjects, LV shape in aortic regurgitation definitely appears asymmetric because of the elongation of the anterior hemiperimeter and the prevailing expansion of the apical and anterolateral regions. These alterations in cavity geometry correlate to the decrease in pump function. According to these results wall motion analysis using the CM showed a greater extension of LV asynergy, while usual methods as the centerline or the radial one indicate a greater damage of the apical regions. Thus, the CM method seems to be a promising tool for wall motion analysis.

Angiocardiography↗

[Transcoronary chemical ablation of ventricular tachycardia in a patient with chronic chagas cardiomyopathy].

A case of recurrent ventricular tachycardia in the setting of chronic chagasic heart disease refractory to conventional antiarrhythmic agents as well as high doses of amiodarone (600 mg/day) is reported. Left ventriculography disclosed an apical aneurysm and a filling defect image suggestive of a thrombus. Sustained monomorphic ventricular tachycardia with the same QRS configuration as "clinical" tachycardia could be induced by means of right ventricular programmed electrical stimulation. The risk of systemic embolization precluded endocardial activation mapping of ventricular tachycardia. Intracoronary cold saline injections were done during induced ventricular tachycardia looking for a coronary artery branch related to the arrhythmogenic substrate. Cold saline mapping results pointed to an apical site of origin. Next step was intracoronary injection of ethyl alcohol in the distal part of the left anterior descending artery leading to a small and uncomplicated myocardial infarction. Control programmed stimulation was unable to reinduce ventricular tachycardia. Clinical outcome was uneventful and there was no recurrence of clinical arrhythmia in 6 months of follow-up.

Catheter Ablation↗

Skin levels of vasoactive intestinal polypeptide in atopic dermatitis.

Atopic dermatitis (AD) can be exacerbated by various factors, including emotional stress, scratching and sweating. The aim of the present study was to evaluate the hypothesis that the inflammatory reaction in AD is also neurogenic. For this purpose, the levels of vasoactive intestinal polypeptide were measured radioimmunologically in whole-tissue homogenates of lesional skin of 13 patients with atopic dermatitis. Radioimmunoassay was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment vasoactive intestinal polypeptide (22-28). Vasoactive intestinal polypeptide immunoreactivity was detected in relatively low amounts in control skin (0.428 +/- 0.08 pmol/g tissue), whereas a marked increase in the peptide was observed in lesional skin of patients with atopic dermatitis (5.62 +/- 1.25 pmol/g tissue). These results seem to suggest that vasoactive intestinal polypeptide could have a pathogenetic relevance in skin lesions of atopic dermatitis.

Adolescent↗

Acute hemodynamic effects of intravenous diperdipine, a new dihydropyridine derivative, in coronary heart disease.

The acute hemodynamic effects of a new dihydropyridine calcium channel blocker, diperdipine, which is suitable for intravenous administration, were studied by right and left cardiac catheterization in 16 patients with coronary heart disease. Diperdipine markedly reduced systemic vascular resistance and improved stroke index and left ventricular ejection fraction. Mean pulmonary artery and wedge pressures were slightly increased as a possible consequence of enhanced venous return, whereas right atrial and left ventricular end-diastolic pressures were not significantly changed. Nevertheless, an increase in preload was clearly indicated by an augmented left ventricular end-diastolic volume index after administration of diperdipine. Left ventricular contractility, which was estimated by the end-systolic pressure-volume ratio and by dP/dt max was not significantly changed, though analysis of individual data suggests a minimally negative inotropic effect. However, such a minor effect on left ventricular contractility was largely counterbalanced by the marked reduction of afterload, which produced a sharp improvement of stroke index. Enhancement of left ventricular ejection fraction and reduction in systemic vascular resistance were inversely and directly correlated to control values. Overall, diperdipine was well tolerated, but one patient had a major untoward reaction that consisted of an ischemic episode that was possibly related to drug administration. In conclusion, intravenous diperdipine appears to be a potent arteriolar dilating agent that does not affect left ventricular contractility.

Calcium Channel Blockers↗

Abnormalities of left ventricular shape in patients with stable angina.

In this study, left ventricular shape was evaluated quantitatively by calculating the power spectrum and the regional curvatures of angiographic outlines as seen in the right oblique anterior projection. Two groups of patients were studied: 16 normal subjects and 16 patients with stable angina who were selected because of normal left ventricular function (normal left ventricular volumes, pressures, ejection fraction and no regional wall motion abnormality at subjective analysis of ventriculograms). The two groups did not differ in terms of mean age of the patients. Regional curvatures were calculated using the Frenet-Serret formula starting from the mitral corner (point 1) and extending to the aortic corner (point 90). The power spectrum was calculated by means of Fourier analysis. The ventricular shape during diastole of the patients with angina differed significantly from that of the normal group in that there was a greater posterobasal curvature; a lower curvature of the inferior wall showing an inward convexity; a greater parietal curvature of the inferoapical region and a minor curvature of the anterobasal region. The power spectrum differed significantly from that of the normal subjects. The 1st and 2nd harmonics were reduced and the 3rd, 4th, 5th and 6th ones increased. The end-systolic contour of the group of patients with stable angina showed a higher amplitude of the 3rd and 5th harmonics and a lower amplitude of the 1st, 2nd, 9th, 10th and 11th harmonics with respect to the group of normal patients. Regional curvatures showed significant differences between the two groups in the antero-basal region. These modifications of left ventricular shape in patients with stable angina did not appear to be related to age and/or heart rate; to abnormalities in hemodynamics and wall motion; or to acute ischemia. Abnormalities of shape in patients with stable angina, therefore, may indicate a remodeling of the left ventricle due to the structural effects (myocardial and/or interstitial) of chronic ischemia.

Adult↗

Effects of diltiazem on postextrasystolic potentiation in coronary heart disease patients.

The effects of the calcium antagonist, diltiazem (D), on left ventricular (LV) response to postextrasystolic potentiation (PESP) were investigated in 15 coronary artery disease patients. Several haemodynamic and LV function parameters, as well as regional wall kinetics, were analysed. During LV angiography, which was performed before and after D administration (0.25 mg kg-1 bolus and 1.4 microgram kg-1 min-1 infusion), programmed atrial stimulation was applied with the sequence: S1-S1 = 600 ms; S1-S2 = 400 ms; S2-S3 = 800 ms. The results indicate that D exerts a mild negative inotropic effect which is more evident in the postextrasystolic beat (postextrasystolic ESP/ESV and dP/dtmax were significantly lower after D) but the postextrasystolic increase of EF is maintained by the effects of the drug on loading conditions of the left ventricle. Our results indicate that both a reduction of afterload and an increase of preload take place after D. The greater preload reserve induced by the drug (EDVI was significantly higher in each patient after D) was associated with a slight increase in left ventricular filling rate, while end-diastolic compliance and pressure did not show significant variations. These results suggest that the increase in left ventricular preload is due to an increase in left atrial driving pressure, an improvement of left ventricular relaxation or both. D does not affect regional wall kinetics either in basal or in the postextrasystolic beat when overall areas are considered, however its effect seems to be related to the degree of basal regional contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neuropeptides in skin from patients with atopic dermatitis: an immunohistochemical study.

The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P-positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y-positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.

Adolescent↗