E. Del Bianco

Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea

Background  Systemic sclerosis (SSc) and morphoea are connective tissue diseases characterized by fibrosis of the skin. Although to date their pathogenesis has not been clearly defined, it is thought that autoimmunity may play a role in the development of the skin lesions observed in both these diseases. As regulatory T cells (Tregs) play a key role in the modulation of immune responses, it has recently been suggested that Treg impairment may lead to the development of autoimmune diseases.

Infiltrating cells, related cytokines and chemokine receptors in lesional skin of patients with dermatomyositis

Background  There have been only two reports on immunophenotypic characterization in the cutaneous lesions of dermatomyositis (DM) that emphasize the importance of the infiltrating CD4+ T lymphocytes.

The comparative effects of tacrolimus and hydrocortisone in adult atopic dermatitis: an immunohistochemical study

Background  While many studies have demonstrated the efficacy and safety of tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have investigated the effects of tacrolimus on inflammatory cells and their cytokine gene expression in patients with AD.

Calcitonin gene-related peptide in the rat kidney: Occurrence, sensitivity to capsaicin, and stimulation of adenylate cyclase

The occurrence, effects and sensitivity to capsaicin and stimulation of adenylate cyclase of calcitonin gene-related peptide (CGRP) in the rat kidney have been investigated. CGRP-like immunoreactivity was higher in the medulla than in the papilla and the cortex. Capsaicin pretreatment significantly reduced CGRP-like immunoreactivity in the medulla and papilla while a small reduction was found in the cortex. CGRP-immunoreactive nerve fibres were observed surrounding blood vessels and occasionally in the vicinity of renal tubules and between the collecting ducts in the papilla. Some CGRP-immunoreactive fibres were also seen in kidneys from capsaicin-pretreated rats. Infusion of capsaicin (1 microM) through the renal artery of isolated and perfused rat kidney increased the CGRP-like immunoreactivity outflow from the venous effluent. This effect exhibited desensitization at the second challenge with the drug. Infusion of either capsaicin (1 microM) or CGRP (1 microM) reduced the increase of perfusion pressure induced by norepinephrine in isolated perfused rat kidney. Plasma protein extravasation was studied in the various regions of the rat kidney following infusion of capsaicin. No significant change was observed in the medulla, papilla or cortex after capsaicin administration. Adenylate cyclase activity was studied in membrane preparations from cortex, medulla and papilla of rat kidney. Cortical and medullary adenylate cyclase was stimulated in a concentration-dependent manner by salmon calcitonin, rat calcitonin and rat CGRP. Salmon calcitonin in these two areas showed half-maximal effective concentration approximately 1000 times lower and maximal stimulation only slightly higher than those of rat calcitonin and rat CGRP. However, in the papilla, only rat CGRP was able to induce a 60% increase of enzyme activity (half-maximal effective concentration, 19 +/- 1.6 nM). It is concluded that CGRP contained in capsaicin-sensitive sensory nerve may exert a local function in discrete areas of the rat kidney.

Regulatory T cells in skin lesions and blood of patients with bullous pemphigoid

Although regulatory T cells (Tregs) are affected in several autoimmune skin diseases, only two studies have been performed in patients with bullous pemphigoid (BP) with contrasting results.

Cellular adhesion molecules in chronic urticaria: modulation of serum levels occurs during levocetirizine treatment.

Background  Some antihistamines are capable of reducing levels of adhesion molecules in wealing tissues of patients with chronic urticaria (CU).

Effect of the GABAB antagonist, phaclofen, on baclofen-induced inhibition of micturition reflex in urethane-anesthetized rats

The effect of intrathecal or intracerebroventricular administration of the GABAB receptor agonist, baclofen, on rhythmic contractions induced by distension of the urinary bladder (micturition reflex) was evaluated in urethane-anesthetized rats. Baclofen inhibited bladder motility acting at central nervous system sites (spinal and supraspinal) with a comparable potency. The inhibitory effect of i.t. baclofen (0.1-10 nmol) was blocked by i.t. phaclofen (200 nmol) while i.c.v. phaclofen did not affect i.c.v. baclofen (0.1-1 nmol). The inhibition of the micturition reflex induced by bladder distension observed after i.t. administration of baclofen was unaffected by systemic capsaicin pretreatment (50 mg/kg s.c., four days before). On the other hand, i.t. baclofen suppressed, in a phaclofen-sensitive manner, the reflex bladder contraction evoked by chemical stimulation (topical capsaicin) of capsaicin-sensitive bladder afferents. Intrathecal baclofen did not affect the hexamethonium-resistant tonic contraction produced by topical application of capsaicin on to the urinary bladder, which is ascribable to local peptide release from sensory nerves. Bladder motility inhibition by i.t. or i.c.v. baclofen (1 nmol) was unchanged by previous administration of p-chlorophenylalanine, indicating that the serotonergic pathways do not play a role in its action. Baclofen (100 microM) suppressed the release of calcitonin gene-related peptide-like immunoreactivity evoked by electrical field stimulation from the dorsal half of the rat spinal cord. This response was also abolished by in vitro capsaicin desensitization or tetrodotoxin, indicating that baclofen suppresses transmitter release from central endings of capsaicin-sensitive primary afferents. The present findings indicate that baclofen acts at both spinal and supraspinal sites to inhibit, with different mechanisms, the micturition reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated circulating CD40 ligand in patients with erythema multiforme and Stevens–Johnson syndrome/toxic epidermal necrolysis spectrum

glands show no abnormality. EN has sometimes been associated with an increase of mucin production. Romer and Taira described a patient with a cutaneous erythematous nodule that had appeared 2 years before, localized on the lower right limb. It contained both eccrine and mucinous elements, and the authors coined the term MEN. Llombart et al. and Park et al. have described identical lesions in two other patients. These three cases of MEN and our patient present similar clinical and histological findings. Our case contributes additional information, in that the MEN lesions showed a distribution following the lines of Blaschko, with an extensive pattern along the lower left limb with multiple nodular lesions, and associated with focal hyperhidrosis. The origin of MEN is not known. The lesions of MEN may be a result of the migration path of clones of genetically identical cells during fetal development, following the lines of Blaschko. However, during adulthood MEN might arise and become evident only after significant stimuli, e.g. growth factors stimulating fibroblasts, which may increase the synthesis of mucin. Our case highlights the hypothesis that this type of hamartomous lesion may be a subgroup of epidermal naevus with eccrine and mucinous differentation, with local or extensive location and with distribution following the lines of Blaschko. The description of more cases of MEN will give us more information in relation to the exact pathogenesis of this particular entity.

Cyclophosphamide-induced cystitis in rats: involvement of capsaicin-sensitive primary afferents.

The involvement of capsaicin-sensitive primary afferent neurons has been investigated in a rat model of cyclophosphamide (CYP)-induced cystitis. CYP (150 mg/kg i.p., 48 h before) was administered in both vehicle- and capsaicin-(50 mg/kg s.c., 4 days before)-treated rats. Some experiments were performed 96 h after bilateral removal of pelvic ganglia (bladder denervation). CYP produced a marked detrusor hyperreflexia which was abolished by capsaicin pretreatment. CYP produced a marked increase in bladder weight and plasma protein extravasation (PPE, measured by Evans blue leakage technique): CYP-induced PPE was reduced by bladder denervation and was aggravated by capsaicin pretreatment. PPE aggravation by capsaicin was abolished by ganglionectomy. The bladder content of calcitonin gene-related peptide, was unaffected CYP. We conclude that CYP-induced decrease in bladder capacity is entirely mediated through stimulation of capsaicin-sensitive bladder afferents. At the time chosen as end point in these experiments, capsaicin-sensitive afferents exert an antiinflammatory influence on CYP-induced cystitis.

Linear IgA disease presenting as prurigo nodularis

Its potential for confusion with skin lesions of systemic candidiasis. Arch Intern Med 1982; 142:2126–9. 8 Rosen T, Schell JB, Orengo I. Anti-inflammatory activity of antifungal preparations. Int J Dermatol 1997; 36:788–92. 9 Faergemann F, Bergbrant IM, Dohse M et al. Seborrhoeic dermatitis and Pityrosporum (Malassezia) folliculitis: characterization of inflammatory cells and mediators in the skin by immunohistochemistry. Br J Dermatol 2001; 144:549–56. 10 Hill MK, Goodfield JD, Rodgers FG et al. Skin surface electron microscopy in Pityrosporum folliculitis: the role of follicular occlusion in disease and the response to oral ketoconazole. Arch Dermatol 1990; 126:181–4.