Born in the Purple: An Exceptional Case of Cutis Marmorata Telangiectatica Congenita

A full-term, 2-day-old female neonate with a congenital non-tender reticular patch that did not disappear with local warming was referred to our department for consultation. The family history as well as the antenatal course and delivery were unremarkable. On examination, we evidenced a fixed, marbled, bluish to deep purple lesion with a fishnet appearance extending over the right side of her body, face, and scalp. There was presence of atrophy of the involved skin, along with ulceration above the right lateral malleolus. Upon blanching, the lesions could not be emptied completely

Born in the Purple: An Exceptional Case of Cutis Marmorata Telangiectatica Congenita

A full-term, 2-day-old female neonate with a congenital non-tender reticular patch that did not disappear with local warming was referred to our department for consultation. The family history as well as the antenatal course and delivery were unremarkable. On examination, we evidenced a fixed, marbled, bluish to deep purple lesion with a fishnet appearance extending over the right side of her body, face, and scalp. There was presence of atrophy of the involved skin, along with ulceration above the right lateral malleolus. Upon blanching, the lesions could not be emptied completely

Multiple Primary Melanomas in a Young Patient

A 45-year-old HIV-negative Caucasian man with no reported past medical history was referred to our Department with a large (7 cm in diameter) oozing nodule on the occipital region of the scalp with spontaneous periodical bloody or purulent discharge. The lesion had appeared over a period of six months, had an irregular color, non-specific dermoscopic features, and resembled squamous cell carcinoma. The physical examination revealed three more atypical melanocytic lesions (on the abdomen, back, and buccal mucosa), and multiple swollen occipital, postauricular, as well as superficial and deep cervical lymph nodes. After clinical evaluation, the patient reported having another in situ melanoma (submammary region) excised 7 years ago. All the lesions were excised and sent for histopathologic examination, which was compatible with primary cutaneous melanoma. Total body computed tomography revealed the presence of multiple visceral metastases, and the patient was referred to an oncologist. He did not consent to proceed to genetic testing

Anticancer Agent Effect and Polychemotherapy Regimens for Malignant Tumor Treatment - A Review

Cancer is a leading cause of millions of deaths worldwide and, despite the improvements in molecular biology, issues concerning how to advance cancer treatment are still relevant. Cancer research must be focused on finding new and efficient chemotherapeutic regimens that can relieve severe side effects caused by conventional treatments. Modern technologies are currently under estimation in clinical trials or have already been introduced into clinical practice. Nowadays cancer therapy is characterized by ineffectiveness and serious side effects, as well as by hope of remission and cure in many cases. Antitumor drugs and radiation have been used as the treatment of choice in some cancer cases, except for the choice of surgery in case of solid tumors. Recently, immunotherapy has emerged as a significant therapeutic alternative, and in many cases, it is the first choice. These therapies can be applied either alone or in combination with other agents. Additionally, gene treatment and nanotechnology are promising methods for cancer treatment as well. The current review presents the progress of cancer treatments, starting with surgery, chemotherapy, radiation and immunotherapy, gene treatment and nanomedicine, giving emphasis to the most common anticancer agents and polychemotherapeutic regimens

Ribonuclease P (RNase P) from human peripheral lymphocytes

Ribonuclease P (RNase P) is the enzyme responsible for the 5΄maturation of the precursor tRNA molecules, participating in tRNA biogenesis and therefore in protein synthesis. It catalyses the endonucleolytic cleavage of a phosphodiester bond in the presence of Mg²⁺ and results in the production of molecules that bear 3΄hydroxyl and 5΄phosphoric ends. Most forms of RNase P are ribonucleoproteins consisting of an essential RNA and protein subunits. The RNA component of the bacterial RNase P was one of the first identified catalytic RNAs. So far, RNase P and the ribosome are the only ribozymes known to be conserved in all kingdoms of life (bacteria, archaea and eucarya). Eykaryotic RNase P activity has been detected in nuclei, mitochondria and chloroplasts and demonstrates great variability in protein subunit composition. Nuclear RNase P has been purified or partially purified from several eukaryotes, primarily from yeast and human cells. In humans, the nuclear holoenzyme consists of one essential RNA, named H1 and ten protein subunits, which are Rpp14, Rpp20, Rpp21, Rpp25, Rpp29, Rpp30, Rpp38, Rpp40, hPop1 and hPop5. It was recently shown that RNA of human RNase P retains traces of catalytic activity. In view of the vital importance of lymphocytes for an effective immune system, we proceeded to the RNase P isolation from human peripheral lymphocytes. The enzyme was purified with cation exchange phosphocellulose chromatography. RNase P was eluted with a linear gradient of 50-500 mM NH₄Cl. Enzyme assays were carried out using an in vitro labeled transcript of Schizosaccharomyces pombe tRNASer gene SupS1. The products of the enzymatic reaction were resolved on a denaturing polyacrylamide 10%, 8 M urea gel and visualized by phosphorimaging in a Fuji FLA-3000 and quantified by using the AIDA software package. Herein, it was investigated the effect of the synthetic retinoids (cisretinoic acid and acitretin), neomycin B, as well as chloroquine diphosphate, on the RNase P activity. Cis-retinoic acid, acitretin and neomycin B exerted a dose-dependent inhibitory effect on RNase P activity from human lymphocytes, while the activity was not affected in the presence of chloroquine diphosphate. A detailed kinetic analysis showed that the inhibition caused by acitretin was of competitive type, whereas that caused by neomycin B was of noncompetitive type. The kinetic constant Km (245 nM) of RNase P activity isolated from lymphocytes for the tRNA maturation reaction is comparable to that of RNase P isolated from normal human epidermal keratinocytes (Km=233 nM). The difference in Vmax values (0.42 pmol/min for the RNase P from human peripheral lymphocytes compared to 2.4 pmol/min for the normal human epidermal keratinocytes) may be due to different enzyme concentration of the two RNase P preparations used for the kinetic analysis. We cannot exclude the possibility that the differences in the Vmax values reflect differences in the protein content of the two enzymes, which may also explain the differential chromatographic behavior. Finally, the isolation of RNase P from human peripheral lymphocytes will enable the study of the possible involvement of this ribozyme in the pathogenetic mechanisms of diverse autoimmune, inflammatory and neoplastic cutaneous disorders and may facilitate the further development of RNase P-based technology for gene therapy of infectious and neoplastic dermatoses.Η ριβονουκλεάση P (RNase P) είναι το ένζυμο που ευθύνεται για την ωρίμανση του 5΄άκρου των πρόδρομων μορίων tRNA συμμετέχοντας έτσι στην πρωτεΐνοσύνθεση. H RNase P καταλύει την ενδονουκλεολυτική θραύση ενός φωσφοδιεστερικού δεσμού παρουσία ιόντων Mg²⁺ παράγοντας προϊόντα με 3΄υδροξυλικά και 5΄φωσφορικά άκρα. Η πλειοψηφία των RNase P ενζύμων που έχουν μελετηθεί μέχρι σήμερα είναι ριβονουκλεοπρωτεΐνες αποτελούμενες από μια RNA και πρωτεϊνικές υπομονάδες. Η RNA υπομονάδα της βακτηριακής RNase P είναι ένα από τα πρώτα καταλυτικά RNA που μελετήθηκαν. Η RNase P και το ριβόσωμα είναι τα μόνα γνωστά ριβοένζυμα που είναι συντηρημένα και στις τρείς φυλογεννετικές περιοχές (βακτήρια, αρχαία και ευκαριώτες). Η ευκαρυωτική RNase P έχει απομονωθεί από πυρήνες, μιτοχόνδρια και χλωροπλάστες και παρουσιάζει μεγάλη ποικιλία στην σύσταση των πρωτεΐνικών υπομονάδων. Η πυρηνική RNase P έχει απομονωθεί από διάφορους ευκαρυωτικούς οργανισμούς και αρχικά από την ζύμη και τον άνθρωπο. Το ανθρώπινο πυρηνικό ολοένζυμο αποτελείται από μία RNA υπομονάδα που ονομάζεται Η1 και δέκα πρωτεϊνικές οι οποίες είναι η Rpp14, Rpp20, Rpp21, Rpp25, Rpp29, Rpp30, Rpp38, Rpp40, hPop1 και hPop5. Πρόσφατα δείχτηκε πως η RNA υπομονάδα της ανθρώπινης RNase Ρ διατηρεί ίχνη καταλυτικής δραστικότητας. Δεδομένης της ζωτικής σημασίας των λεμφοκυττάρων στην ακεραιότητα του ανοσολογικού συστήματος και στην παθογένεια ευρέος φάσματος δερματολογικών και μη νοσημάτων, σκοπός της παρούσας εργασίας ήταν η ανάπτυξη μεθοδολογίας για την απομόνωση και τον καθαρισμό της. Δεδομένης της ζωτικής σημασίας των λεμφοκυττάρων στην ακεραιότητα του ανοσολογικού συστήματος και στην παθογένεια ευρέος φάσματος δερματολογικών και μη νοσημάτων, σκοπός της παρούσας εργασίας ήταν η ανάπτυξη μεθοδολογίας για την απομόνωση και τον καθαρισμό της RNase P από περιφερικά λεμφοκύτταρα υγιών μαρτύρων, ο προσδιορισμός της ενζυμικής της δραστικότητας, καθώς και η μελέτη της in vitro επιδράσεως δύο συνθετικών ρετινοειδών, του 13-cis ρετινοϊκού οξέος και της ασιτρετίνης, της αμινογλυκοσίδης νεομυκίνης Β, όπως και της διφωσφορικής χλωροκίνης στην δραστικότητα της λεμφοκυτταρικής RNase P. Το ένζυμο καθαρίστηκε με τη χρήση κατιοντοανταλλακτικής χρωματογραφίας φωσφοκυτταρίνης. Η RNase P εκλούστηκε με γραμμική βαθμίδωση συγκέντωσης NH₄Cl από 50-500 mΜ. Το μέγιστο της δραστικότητας εκλούστηκε σε 285mM NH₄Cl, σε αντίθεση με το ένζυμο της RNase P από τα επιδερμιδικά κερατινοκύτταρα, του οποίου το μέγιστο της δραστικότητας εκλούεται σε 190mM NH₄Cl. Τα πειράματα για την ανίχνευση του ενζύμου πραγματοποιήθηκαν με την χρήση ενός ραδιενεργά σημασμένου in vitro μεταγραφήματος του tRNA της σερίνης από τον Schizosaccharomyces pombe (SupS1). Τα προϊόντα της ενζυμικής αντίδρασης αναλύθηκαν σε αποδιατακτικό πήκτωμα πολυακρυλαμιδίου 10%, 8Μ ουρίας, έγιναν ορατά μέσω Phosphorimager FLA 3000 (FUJIFILM) και ποσοτικοποιήθηκαν με το πρόγραμμα PCBAS/AIDA (Raytest). Μετά από μελέτη της επίδρασης των συνθετικών ρετινοϊδών (13-cis ρετινοϊκό οξύ και ασιτρετίνη) και της νεομυκίνης Β στην δραστικότητα της RNase P, προέκυψε ότι το 13-cis ρετινοϊκό οξύ (ισοτρετινοΐνη), η ασιτρετίνη και η νεομυκίνη Β προκαλούν μια δοσοεξαρτώμενη αναστολή της δραστικότητας της RNase Ρ των ανθρωπίνων λεμφοκυττάρων. Η διφωσφορική χλωροκίνη δεν επηρεάζει τη δραστικότητα της λεμφοκυτταρικής RNase P. Λεπτομερής κινητική ανάλυση έδειξε πως η αναστολή που προκαλείται από την ασιτρετίνη είναι συναγωνιστικού τύπου, ενώ αυτή από την νεομυκίνη Β είναι μη συναγωνιστικού τύπου. Η κινητική σταθερά Km (245 nM) της λεμφοκυτταρικής RNase P είναι παρόμοια με εκείνη της RNase P που απομονώθηκε από φυσιολογικά επιδερμικά κερατινοκύτταρα (Km=233 nM). Η διαφορά, όμως, της σταθεράς Vmax μεταξύ των δυο αυτών ενζύμων (0.42 pmol/min για τη λεμφοκυτταρική RNase P και 2.4 pmol/min για την RNase P από επιδερμικά κερατινοκύτταρα) μπορεί να οφείλεται στη διαφορετική συγκέντρωση ενζύμου που χρησιμοποιήθηκε για την κινητική μελέτη. Δεν μπορεί παρόλα αυτά να αποκλειστεί η πιθανότητα, αυτή η διαφορά της σταθεράς Vmax μεταξύ των δυο ενζύμων να αντανακλά διαφορές στην πρωτεϊνική τους σύσταση, γεγονός που επίσης εξηγεί τη διαφορετική χρωματογραφική συμπεριφορά τους. Συμπερασματικά, η απομόνωση της RNase P από ανθρώπινα περιφερικά λεμφοκύτταρα καθιστά δυνατή τη μελέτη της πιθανής ανάμιξης αυτού του ριβοενζύμου στους παθογενετικούς μηχανισμούς διαφόρων αυτοάνοσων, φλεγμονωδών και νεοπλασματικών δερματοπαθειών και μπορεί να διευκολύνει τη περαιτέρω ανάπτυξη της βασιζομένης στην RNase P τεχνολογίας για τη γονιδιακή θεραπεία δερματικών και μη παθήσεων

Malacoplakia of the skin: overview of a rare clinical entity

Background: Malacoplakia is a rare acquired, infection-related granulomatous disorder, that may affect many systems, but typically occurs in the urinary tract. Cutaneous involvement is less prevalent, and most commonly presents with a perianal or genital region localization. Cutaneous malacoplakia is believed to be caused by an acquired bactericidal defect of macrophages in the setting of chronic infections and immunocompromised states. A diagnosis of cutaneous malacoplakia should be considered when encountering non-specific granulomatous lesions that are refractory to treatment. Histologic findings are marked by the presence of foamy macrophages containing the pathognomonic Michaelis-Gutman bodies. Objectives. The aim of this review is to discuss the current perspectives on the pathophysiology, clinical features, diagnosis, and treatment of this disease. We would also like to emphasize that the integration of clinical information, microscopic findings, and exclusion of other cutaneous granulomatous processes is necessary to accurately diagnose this exceedingly rare disease and provide opportunity for therapeutic intervention. Patients/Methods. Data for this work were collected from the published literature and textbooks. Results. Combined surgical excision and protracted antibiotic courses appear to have the highest success rate. Antibiotics should be culture specific, but drugs that easily permeate the macrophages appear to be the best choice

Acremonium nail bed mycetoma masquerading as subungual squamous cell carcinoma

Acremonium is a large fungal genus that is comprised of approximately 150 species, found ubiquitously in nature. Although the majority are recognized as being saprophytes in soil and pathogens of plants, several species are emerging as causative agents of a variety of human infections, including mycetomas. Herein, we present a young man that was referred to our department with a painful subungual mass that developed following traumatic inoculation of Acremonium spp. In recent years, the role of Acremonium spp. has been increasingly recognized in localized infections, such as mycetoma, in humans. Other locally invasive as well as disseminated infections are also described. Optimal treatment of Acremonium spp. mycetoma is not well defined owing to the rarity of cases, thus posing a therapeutic challenge

Partial purification and characterization of RNase P from human peripheral lymphocytes.

Ribonuclease P (RNase P) is ubiquitous and essential Mg(2+)-dependent endoribonuclease that catalyzes the 5'-maturation of transfer RNAs. RNase P and the ribosome are so far the only ribozymes known to be conserved in all kingdoms of life. Eukaryotic RNase P activity has been detected in nuclei, mitochondria and chloroplasts and demonstrates great variability in sequence and subunit composition. In the last few years we have developed methodologies and pursued projects addressing the occurrence, distribution and the potential physiological role of RNase P in human epidermal keratinocytes. In view of the vital importance of lymphocytes for an effective immune system and their successful application after transfection with RNase P-associated external guide sequences in gene therapy, we concerned ourselves with the isolation and characterization of RNase P of peripheral human lymphocytes. We developed a method described herein, that will enable the study of the possible involvement of this ribozyme in the pathogenetic mechanisms of diverse autoimmune, inflammatory and neoplastic cutaneous disorders and may facilitate the further development of RNase P-based technology for gene therapy of infectious and neoplastic dermatoses.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

Nipple candidiasis and painful lactation: an updated overview

Nipple pain and discomfort during or after breastfeeding remains one of the most common reasons for premature cessation of lactation among the affected women. The belief that yeasts, and especially Candida spp., are responsible for such symptoms is highly supported by many physicians, midwives, or lactation specialists, but is also viewed with scepticism by other health care providers. The aim of this paper is to provide an updated report of the evidence against, as well as in favour of, the “Candida hypothesis”. Several studies have documented that lactating women with symptoms such as nipple soreness, with or without radiating breast pain, are more likely to test positive for Candida spp. than non-symptomatic women. However, its role as an undisputable aetiopathogenic factor for infection in these cases cannot always be established. Physicians should evaluate thoroughly such patients, because early and correct recognition of the underlying problem can prevent phenomena of early weaning

Real-world clinical outcomes of treatment with brodalumab in patients with moderate-to-severe psoriasis: a retrospective, 24-month experience from four academic dermatology centers in Greece

Objective To assess the real-world clinical treatment outcomes with brodalumab in patients with moderate-to-severe plaque psoriasis in Greece. Materials and methods This was a longitudinal, retrospective, real-world analysis of data from medical records of 106 patients with moderate-to-severe plaque psoriasis, treated with brodalumab for up to 24 months at four University Dermatology Centers in Greece. Efficacy assessments of psoriasis severity [Psoriasis Area and Severity Index (PASI) and Body Surface Area affected (BSA) scores] and its impact on patients’ quality of life (QoL) [Dermatology Life Quality Index (DLQI) score] were evaluated at different timepoints up to 24 months. Results Treatment with brodalumab reduced both mean PASI (14.0–1.5, p < .001) and BSA scores (21.6–2.5, p < .001) across all visits. This effect was accompanied by reduction in mean DLQI score (12.8–2.1, p < .001) across all visits compared with baseline. Moreover, therapeutic efficacy was affected by prior biologic treatment exposure, as biologic naïve patients had greater reductions in all scores from baseline following treatment with brodalumab (numerical for mean PASI, significant for mean BSA and DLQI scores). Conclusion Brodalumab is effective long term, improving disease severity and health-related QoL in patients with moderate-to-severe plaque psoriasis in a real-world setting