Claudia Costa

Transglutaminase-synthesized spermine derivative of substance P recognizes rat portal vein neurokinin-3 receptors

The effects of the transglutaminase-synthesized polyamine derivatives of Substance P (SP) have been further characterized by their ability to contract in vitro the rat portal vein strip (RPV), a pharmacological preparation particularly rich in NK-3 receptors. The effects of selective agonists of NK-1, NK-2 and NK-3 receptors [Sar9,Met(O(2))11]SP, beta-Ala8 NKA(4-10), and senktide respectively, were also evaluated by measuring RPV concentration-response curves. Peptide [GR-82334 (NK-1) and MEN-10,376 (NK-2)] and nonpeptide [WIN 51,708 (NK-1) and SR 142801 (NK-3)] NK receptor antagonists were used to confirm the participation of the different NK receptors to contractile response. Our results demonstrated that the spermine derivative of SP (Spm-SP), previously shown to be unable to recognize NK-1 and NK-2 receptors in some bioassays, contracts RPV (EC50 = 588 nM) better than the native neuropeptide (EC50 = 1120 nM). A pretreatment with thiorphan, an inhibitor of neutral endopeptidases, significantly reduced such a difference. While this inhibitor shifts the SP concentration-response curves to the left (EC50 = 720 nM) the action of Spm-SP and [Sar9,Met(O(2))11]SP were completely thiorphan-resistant. In the absence of thiorphan we found the following rank order of potency: senktide > > beta-Ala8 NKA(4-10) > [Sar9,Met(O(2))11]SP = Spm-SP > SP. Among the mentioned NK receptor antagonists, only the selective NK-3 receptor antagonist, SR 142801, shifted to the right Spm-SP and [Sar9,Met(O(2))11]SP concentration-response curve, showing pKB values of 5.84 and 5.88, respectively. Therefore, the reported results suggest that the introduction of a Spm moiety into the SP alters the parent peptide molecule by increasing its affinity for NK-3 receptors and/or by preventing its degradation by some proteolytic enzymes.

Transglutaminase-mediated amine incorporation into substance P protects the peptide against proteolysis in vitro☆

The in vitro metabolism of transglutaminase-synthesized substance P analogs has been characterized comparing their stability to that of the parent peptide. The major metabolites have been purified and their structures elucidated by mass spectrometry. Our results demonstrated that gln5 spermidine and spermine analogs of substance P possess an enhanced resistance to the action of proteases. Moreover spermine, a large size hydrophilic compound, specifically prevented the hydrolysis at Phe7-Phe8 bond.

Dermoscopy Pattern, Histopathology and Immunophenotype of Primary Cutaneous B-Cell Lymphoma Presenting as a Solitary Skin Nodule

Importance: To date, no dermoscopic features have been described for the diagnosis of primary cutaneous B-cell lymphoma (PCBCL). This tool might be helpful for the clinical differential diagnosis in the context of single erythematous nodules of the skin. Observations: Ten cases of PCBCL, presenting clinically as solitary red/pinkish nodules, were retrospectively retrieved. Patient data were collected along with dermoscopic and histopathological features of each lesion. Most lesions (9/10) showed white circles with a salmon-colored background/area (6 lesions), scales (7 lesions), arborizing vessels (5 lesions) or a polymorphous vascular pattern (2 lesions). Histology revealed a cutaneous marginal zone lymphoma in 6 lesions, a follicle center lymphoma in 2 lesions and a diffuse large B-cell lymphoma in 2 lesions. Conclusions and Relevance: Dermoscopic examination may be helpful for improving the clinical recognition of PCBCL although skin biopsy remains mandatory.

Transglutaminase-Synthesized γ-(Glutamyl5) Spermidine Derivative of Substance P Is a Selective Tool for Neurokinin-2 Receptors Characterization

The ability of transglutaminase-synthesized 1,3-diaminopropane, spermidine (Spd), spermine (Spm), and monodansylcadaverine gamma-(glutamyl5)derivatives of substance P (SP) to produce bronchoconstriction was investigated. In urethane-anaesthetized guinea pigs, intravenous injections of SP derivatives contracted differently bronchial smooth muscle and caused hypotension. The most effective bronchoconstrictor among SP analogs was the gamma-(glutamyl5)Spd derivative of SP (Spd-SP; EC50 = 5.3 nmol/kg), which was more potent than the native peptide (EC50 = 26.5 nmol/kg). In contrast, the gamma-(glutamyl5)Spm derivative of SP (Spm-SP) was found completely unable to cause bronchoconstriction and was significantly less effective than SP in determining hypotension. The contractile effect of Spd-SP and Spm-SP was investigated in vitro on rat isolated colon, a well-characterized preparation rich in NK2 receptors. In addition, Spd-SP was tested on the endothelium-denuded rabbit pulmonary artery (RPA) and the hamster isolated trachea (HT), both tissue preparations containing only a single functional receptor subtype (NK2A and NK2B, respectively). The results obtained showed that Spd-SP recognizes NK2 receptors occurring on rat isolated colon more effectively (EC50 = 11 nM) than the native peptide (EC50 = 45 nM). Conversely, Spm-SP evokes a contractile response less effective than that elicited by SP (EC50 = 312 nM). Furthermore, Spd-SP (0.1-10 microg kg(-1)) produced a concentration-dependent contraction of both HT and RPA, exhibiting a potency respectively 12 and 30 times higher than SP in contracting HT and RPA. Our results indicate that the introduction of a Spd moiety at the level of glutamine-5 of SP gives rise to an analog that possesses a different capability to recognize NK2 receptors than the parent peptide. Moreover, since Spd-SP seems to contract more effectively RPA than HT, we conclude that it preferentially recognizes the NK2A receptor subtype.

Giant Congenital Melanocytic Naevus with Proliferative Nodules Mimicking Congenital Malignant Melanoma: A Case Report and Review of the Literature of Congenital Melanoma

Congenital malignant melanoma (CMM) is a rare condition that is defined as malignant melanoma recognized at birth. CMM may develop in utero in one of three ways: (1) transmission by metastasis through the placenta from a mother with melanoma; (2) primary melanoma arising within a giant congenital melanocytic naevus (GCMN); (3) primary de novo cutaneous CMM arising in utero. CMM can be confused clinically and histologically with benign proliferative melanocytic lesions such as giant congenital nevi. We describe the case of a patient presenting a GCMN with proliferative nodules, clinically and dermoscopically resembling a CMM, demonstrating the importance of caution in making a diagnosis of MM and highlighting the possibility that benign lesions as GCMN can mimic a malignant melanoma in this age group.

Clinical, dermoscopic and histological features of a Merkel cell carcinoma of the hand.

BACKGROUND Merkel cell carcinoma (MCC) is a rare and typically aggressive form of skin cancer. The benign appearance of the tumor usually on exposed skin parts, contrasting with its extensive microscopic invasion, can delay timely diagnosis. MAIN OBSERVATIONS We report a case of a 71-year-old man with a slowly progressive nodule on the left hand. CONCLUSION At the dermoscopic examination, the presence of a polymorphous vascular pattern, including milky-red areas may constitute an additional clinical clue to accurately diagnose this rare tumor. Clinical, dermoscopic and histological features are discussed.

Subcorneal Pustular Dermatosis in Childhood: A Case Report and Review of the Literature

Subcorneal pustular dermatosis (SCPD, also known as Sneddon-Wilkinson disease) is a rare, benign, chronic, sterile pustular eruption which usually develops in middle-age or elderly women; it is rarely seen in childhood and adolescence. The primary lesions are pea-sized pustules classically described as half-pustular, half-clear flaccid blisters. Histologically the most important feature is a subcorneal accumulation of neutrophils with the absence of spongiosis or acantholysis, although acantholysis may be reported in older lesions. In this paper we present the case of a 7-year-old boy diagnosed with SCPD based on the characteristic clinical and histological features. Dapsone has been successfully used in the treatment of the disease.

Tungiasis: Case Report of a Traveller to Kenya

Tungiasis is a neglected parasitic skin disease caused by the permanent penetration of the female sand flea Tunga penetrans (also called jigger flea) into the skin of its host. Growing urbanisation, improved housing and the use of appropriate footwear have presumably led to an overall reduction of the occurrence of this ectoparasitosis within the last few decades. However, it is still highly prevalent in regions where people live in extreme poverty, such as in many Latin American and African countries [1, 2]. We report the case of a 44-year-old woman who returned from an excursion trip to Kenya’s savannah with an infection of T. penetrans located on her right big toe around the nail. The natural history, pathology, epidemiology, diagnosis, therapy and control of this parasitic skin disease are discussed [1].

Bullous Fixed Drug Eruption Induced by Paracetamol: Report of a Pediatric Case

Drug eruptions are among the most common adverse drug reactions, affecting approximately 3% of hospitalized patients. A fixed drug eruption (FDE) is a distinct drug-induced reaction pattern that characteristically recurs at the same skin or mucosal site. We report a case of a 2-year-old girl with bullous FDE due to Tachipirina syrup, a preparation containing paracetamol, a commonly used nonsteroidal anti-inflammatory drug in Italy.

Dermoscopy of uncommon variants of dermatofibrosarcoma protuberans

(Fig. 2c). The dermoscopic aspect of a roundish structure that goes out and into a sanguinolent ulcer is typical of myiasis due to Dermatobia hominis that is inside the skin and extrudes intermittently. This parasite is common in tropical American countries where its eggs are deposited into human skin by phoretic insects and penetrate via hair follicles or through bite wounds. In our case, we covered the lesion with an occlusive dressing to interrupt the oxygen support, and the larva was extracted surgically after 8 h. Reflectance confocal microscopy allowed to better understand what was seen under dermoscopy. RCM images perfectly correlated with dermoscopy showing the transversal roundish section of the parasite characterized by a hyper-reflective external coating, a peripheral intermediate reflective ring (corresponding to the yellowish ring seen under dermoscopy) and a hyporeflective central part (corresponding to the brownish part seen under dermoscopy) (Fig. 2b). Notably, RCM also showed a polycyclic structure (Fig. 2c) corresponding to the section of the valves of the breathing spiracle that have been clearly identified only once under dermoscopy and described as a ‘two bird’s feet-like structure’. Microscopic examination with chlorazol black coloration showed the body of the parasite with an outer cuticle and a less dense inner part (Fig. 2d,e) that explained the different reflectance under RCM. Moreover, it showed the breathing spiracle of the posterior part of the parasite (Fig. 2f). HDOCT did not allow to show the parasite, probably because differently from RCM and dermoscopy it is more difficult to create a close contact between the large tip of this device and the scalp in order to induce the ascent of the larva for breathing. In conclusion, RCM can identify Dermatobia hominis and can be used to better understand the dermoscopic features of this parasitosis as it has been carried out for other cutaneous parasites.