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P Cappugi

Publications and source records attributed to P Cappugi.

36 records · Page 2Linked to original sources

The role of histamine in platelet aggregation by physiological and immunological stimuli.

BACKGROUND: Platelets participate in allergic and inflammatory processes beside their role in haemostasis and thrombosis. This paper reports the level, the uptake, the metabolism and the release of histamine in human platelets. The effects of exogenous histamine, as well as the receptor and signal transduction of these effects, are also described. METHODS: Purified suspensions of platelets, prepared from healthy volunteers and from atopic patients, were exposed in vitro to physiological and immunological stimuli. Platelet aggregation was measured by the increase in light transmission; histamine content and release, as well as cytosolic free Ca2+ concentration, were measured fluorimetrically. Platelet histamine forming capacity, and the uptake of exogenous histamine, were measured with a radioisotopic method. RESULTS: Human platelets contain 72.5 +/- 9.6pmoles of histamine x 10(9) platelets, and their capacity to form histamine is 18.7 +/- 3.5pmoles h(-1)g(-1) protein, which is reduced by alpha-fluoromethylhistidine (10(-5) M) a selective inhibitor of the specific histidine decarboxylase. Human platelets take up the preformed amine by a calcium and energy-dependent process, and the uptake of histamine is reduced by mepyramine, an H1-receptor antagonist, and N,N-diethyl-2-[4-(phenylmethyl) phenoxyl] ethanamine (10(-6) M), a blocker of intracellular histamine receptors. Histamine is also metabolized by human platelets. The exposure of platelets to thrombin (10-60 mUml(-1)) produced a progressive aggregation, associated with histamine release. The same is observed in platelets isolated from atopic patients exposed to anti-IgE antibodies. Exogenous histamine dose-dependently potentiates the aggregation induced by physiological and immunological stimuli. In resting platelets cytosolic calcium level (207 +/- 4.2 nM/10(8) platelets) is increased by thrombin as well as by anti-IgE; this effect is potentiated by 10(-5) M histamine. CONCLUSIONS: The synergistic effect between histamine and other monoamines on platelet aggregation may explain some aspects of allergic vasculitis in which platelet aggregation is present.

Blood Platelets↗

Possible involvement of neuropeptidergic sensory nerves in alopecia areata.

Alopecia areata (AA) is a dermatosis involving the sudden occurrence of bald patches on the scalp. Although the aetiology is unknown, experimental data indicate that cutaneous microcirculation plays an important role. The skin is richly innervated by neuropeptidergic sensory nerves that help regulate microvascular circulation. This study shows a reduction of cutaneous levels of substance P and calcitonin gene-related peptide (CGRP) but not of vasoactive intestinal polypeptide in scalp biopsies from patients with AA. Laser-Doppler flowmetry was used to study microcirculation of the scalp. Results indicate that patients with AA have lower basal blood flow and greater vasodilatation following intradermal CGRP injection than control subjects. A vascular hyper-reactivity to vasodilatatory substances such as neuropeptides, probably because of the lack of these substances, is hypothesized.

Adolescent↗

The effects of repeated dermal application of capsaicin to the human skin on pain and vasodilatation induced by intradermal injection of acid and hypertonic solutions.

1. The effect of repeated capsaicin application on the skin of the volar surface of the forearm on the pain sensation and on the increase in blood flow induced by intradermal injection of low pH media or hypertonic solutions was investigated in 13 healthy volunteers. 2. Low pH media (4, and 2.5) were obtained by adding HCl to 0.9% saline. Hypertonic solutions (300 and 600 mM) were obtained by adding NaCl to pH 7.4, 0.9% saline. Capsaicin (1% in 50% ethanol) was painted on the volar skin of one forearm, chosen at random, for 7 days. The contralateral forearm was treated with the capsaicin vehicle. Pain was assessed by a visual analogue scale and skin blood flow by a laser doppler flowmeter. 3. Pain sensation and increase in blood flow (both peak and area under the curve) induced by low pH media were markedly reduced in the capsaicin pretreated side. Capsaicin pretreatment also reduced the increase in blood flow, but did not affect the pain response induced by hypertonic saline solutions. 4. Repeated application of capsaicin to the human skin inhibits both the sensory (pain) and 'efferent' (vasodilatation) responses induced by low pH media, whereas it reduces the vasodilatation, but not the pain caused by hypertonic media. 5. Repeated application of capsaicin to the human skin, a therapy used in various diseases, discriminates between sensory, but not 'efferent' responses induced by different stimuli.

Acids↗

Substance P provokes cutaneous erythema and edema through a histamine-independent pathway.

Substance P is a neuropeptide (contained in/and released from the A delta and C nerve fibers of the skin), which provokes erythema, edema, and pruritus after intradermal injection. Local pretreatment with capsaicin produces decreased substance P-dependent erythema, with edema similar to that observed before pretreatment with capsaicin. We injected histamine and in a parallel experiment, substance P in five volunteers before and after local treatment with capsaicin, with 48/80, after 5 days of hydroxyzine. The injection of SP provoked erythema centered by a wheal. After treatment with 48/80, SP provoked increased erythema and a wheal. After hydroxyzine treatment, the injection of histamine produced no erythema or edema in four of the five subjects, while SP provoked erythema in all five subjects and edema similar to that observed before treatment with hydroxyzine. These data support the hypothesis that substance P provokes erythema and edema both with histamine-dependent and histamine-independent pathways.

Adult↗

[Erythrodermic sarcoidosis].

Cutaneous involvement is relatively frequent in patients with sarcoidosis. The histologic evidence of typical non-caseating granulomas differentiates specific from non-specific skin lesions. Among specific cutaneous lesions of sarcoidosis, erythroderma is exceedingly rare. We report here a case of erythrodermic sarcoidosis. The differential diagnosis and the possible correlation with cutaneous T-cell lymphomas are discussed.

Aged↗

[Preliminary experiences with chemotactic activity of CGRP using the skin window test].

The neuropeptide CGRP (Calcitonin Gene-Related Peptide) develops in sensory fibers of the human skin a series of well proven biological effects and seems particularly correlated with the neurogenic inflammation. In the site of intradermic injection of 50 pmol of CGRP, neutrophilic inflammation was documented. For this reason we have studied using the skin window test the chemotactic actions of this neuropeptide in vivo. The apposition of CGRP (12.5 pmol) on the abraded skin modifies neutrophilic egress, increasing that effect in a significant way in comparison with controls. The action on neutrophils of CGRP helps to explain the importance of this neuropeptide in the genesis of the "Neurogenic inflammation".

Calcitonin Gene-Related Peptide↗

Langerhans cells are not damaged in contact allergic reactions in humans.

Fifteen biopsies from contact allergic reactions in sensitized patients were taken at different time intervals after application of simple chemicals. Two different procedures for electron microscopy were done. No signs of damage were ever seen in Langerhans cells. The authors are therefore of the opinion that there is still no proof for a target role of Langerhans cells in contact allergic reactions in humans.

Cobalt↗

Macrophage-T lymphocyte relationships in man's contact allergic reactions.

Seventeen biopsies from contact allergic reaction sites in sensitized patients were studied by electron microscopy and immunocytochemistry. Very intimate appositions of macrophages to T lymphocytes were frequently observed in the dermis at 6, 8 and 12 hours after application of the allergen. Such juxtapositions were seen less frequently after 24, 48 and 72 hours. These appositions seem to indicate that macrophages play an antigen-presenting role in human contact allergic reactions, as Langerhans cells seem to do.

Allergens↗

The biosynthesis of prostaglandins in psoriatic skin.

The biosynthesis of prostaglandins (PGs) was studied in biopsy material taken from 8 psoriatics and 7 healthy controls. The psoriatic skin showed a statistically significant reduction in the capacity for PG synthesis: in psoriatic skin PGE2 was 301 +/- 74 ng/g wet weight and PGF2 alpha 425 +/- 89 ng/g wet weight, whereas in healthy skin the synthesizing capacity of PGE2 was 507 +/- 45 ng/g wet weight and of PGF2 alpha 730 +/- 206 ng/g wet weight.

Humans↗

Somatostatin treatment of psoriatic arthritis.

Eighteen patients with psoriatic arthritis were treated for 48 hours with an infusion of somatostatin 250 micrograms/hr diluted in a 5% glucose solution. This therapy led to a reduction of joint pain and satisfactory clearing of cutaneous lesions immediately after treatment in eight patients, less marked results in four, and null in four. Two patients were dropped from the study because of negative side effects during administration of the drug. Fifteen days after treatment, the clearing of lesions and joint pain reduction were even more pronounced. The most encouraging results were obtained on erythrodermic and large plaque psoriasis and on the polyarticular involvement. We suggest that the use of this drug, whose side effects are discussed, should be limited to patients with polyarthritis showing severe cutaneous involvement.

Adult↗