67 research outputs found
EFFECTS OF A PSORIATIC INFLAMMATORY MICROENVIRONMENT ON KERATINOCYTE MORPHOLOGY IN 3D AND 2D BIOLOGICAL EXPERIMENTAL MODELS OF NORMAL HUMAN SKIN
No full textThe interplay between proinflammatory circulating cytokines and keratinocytes is a crucial event in the development and progression of psoriatic lesions. However, the early phases of the pathogenesis of psoriasis are still to be elucidated, in particular regarding the epidermal barrier. A pivotal role is played by tight junctions (TJs), i.e. claudin-mediated intercellular attachment structures, localized in the upper granular layer. A barrier impairment associated to an alteration in TJ proteins is described in psoriasis as a response to a proinflammatory microenvironment. We investigated by immunofluorescence analysis the modulation of the expression of claudin 1 (CLDN-1), a transmembrane integral TJ protein, and of Zonula Occludens 1 (ZO-1), a scaffold plaque protein, after the incubation with MIX, a combination of interleukin (IL)-17, IL-22, IL-23, tumor necrosis factor (TNF)-alpha, for 24 (T24) and 48 (T48) hours. We considered as experimental models the standardized 3D organotypic cultures of normal human skin (n=7) and in vitro cultures of primary normal human keratinocytes (n=3) in basal or differentiating cell growth conditions. On skin bioptic samples, ultrastructural analysis by transmission electron microscopy (TEM) was performed. In control skin samples, CLDN-1 immunopositivity increased from the basal layer upwards, but its expression was early reduced in the basal and suprabasal layers starting from T24 in MIX-incubated group. At this time point, ZO-1 expression in control samples increased gradually, starting from the basal layers towards the epidermal surface and the incubation with MIX induced its immunopositivity in the basal and suprabasal layers. At T24, CLDN-1 expression was unaffected by MIX in undifferentiated and also calcium- differentiated keratinocytes. Unexpectedly, undifferentiated cells relocated ZO-1 at cell-cell contact points after the incubation with MIX, and in calcium-differentiated keratinocytes, ZO-1 synthesis was stimulated, too. By TEM, after MIX incubation, the overall architecture of the epidermal compartment was maintained, but apoptosis and enlargement of intercellular spaces were evident.
The present results strongly suggest that the i) broadening of ZO-1 expression and ii) the downregulation of CLDN-1, typical features of psoriasis, can be induced as early as 24 hours in both models, suggesting that they represent a valid experimental approach.
To complete this study, the effect of this microenvironment on keratinocyte proliferation and differentiation will be investigated, obtaining further insights into the early processes leading to the formation/progression of psoriatic plaques.
Donetti E, Cornaghi L, Gualerzi A, Baruffaldi Preis FW, Prignano F. An innovative three-dimensional model of normal human skin to study the proinflammatory psoriatic effects of tumor necrosis factor-alpha and interleukin-17. Cytokine; 2014; 68:1-8.
Donetti E, Cornaghi L, Arnaboldi F, Ricceri F, Pescitelli L, Maiocchi M, Carriero F, Baruffaldi Preis FW, Prignano F. Epidermal barrier reaction to an in vitro psoriatic microenvironment. Exp Cell Res; 2017; 15:180-188.
Donetti E, Lombardo G, Baruffaldi Preis FW, Cornaghi L, Pescitelli L, Prignano F. 3D skin model to investigate the early epidermal morphological psoriatic features. J Transl Sci; 2019; doi: 10.15761/JTS.1000361
Riva F, Casasco A, Nespoli E, Cornaglia AI, Casasco M, Faga A, Scevola S, Mazzini G, Calligaro A Generation of human epidermal constructs on a collagen layer alone. Tissue Eng; 2007; 13: 2769-79.
Riva F, Casasco A, Casasco M, Calligaro A, Cornaglia AI. Growth and stratification of epithelial cells in minimal culture conditions. Methods Mol Biol; 2010; 585:25-43
Therapeutic Algorithm for Congenital Ptosis Repair with Levator Resection and Frontalis Suspension : Results and Literature Review
No full textBackground: Several treatments have been described for the treatment of congenital ptosis, but there are few studies that analyze the effectiveness of a therapeutic approach rather than a single technique. Aims: In this study, we aim to evaluate the effectiveness of our therapeutic algorithm, which relies on levator muscle resection and frontalis suspension with silicone rods, polytetrafluoroethylene (PTFE), or autologous fascia lata. Methods: We retrospectively analyzed all patients affected by congenital ptosis who underwent corrective surgery at a single department between January 1998 and January 2016. Results: A total of 116 procedures were performed in 86 patients, accounting for 35 levator resections, 67 frontalis suspensions, and 14 revisions. A satisfactory result was observed in 65 cases after one procedure (75.6%). Complications occurred in 13 cases after primary surgery (15.1%). Ptosis relapse was observed in 25 cases after primary procedure (21.5%). Frontalis suspension displayed a higher number of complications than levator resection (22.2% vs 3.1%, p=0.02). Conclusion: Our therapeutic algorithm was effective in 75.6% after one procedure. Frontalis suspension procedures encountered a higher rate of complication than levator resection. Fascia lata should be preferred to silicon rods whenever possible due to the lower recurrence rate. These issues confirm the therapeutic algorithm, although larger prospective studies are necessary to validate our approach
Variabili predittive di insoddisfazione postoperatoria a seguito di interventi di chirurgia estetica
No full textil metro fondamentale con cui misurare l’outcome degli interventi
di chirurgia estetica. Essa tende a essere condizionata
da variabili socio-demografiche, anamnestiche e soprattutto
psicopatologiche su cui, al momento, non esiste un consenso.
Obiettivo dello studio è determinare il grado in cui le suddette
variabili possano ritenersi predittive di insoddisfazione. Le
variabili cliniche valutate sono: tratti patologici di personalità,
narcisismo covert, entità del disagio relativo all’immagine
corporea.
Metodi: il campione è risultato composto da 77 soggetti
(91,3% F) tra i 18 e i 57 anni di età sottoposti a diversi tipi di
interventi di chirurgia estetica presso due ospedali milanesi,
tra il 2009-2010. È stata impiegata una batteria di questionari
finalizzata alla rilevazione delle variabili di interesse.
Risultati: tra le variabili considerate, i migliori predittori
dell’insoddisfazione post-operatoria risultano: precedenti procedure
estetiche chirurgiche, la gravità e la precocità dell’insorgenza
del disagio relativo all’immagine del corpo, il numero
dei tratti patologici della personalità in generale e quelli
riconducibili ai disturbi del cluster B in particolare. Esse risultano
inoltre correlate a motivazioni estrinseche e aspettative
irrealistiche rispetto all’esito dell’intervento.
Conclusioni: i dati supportano l’utilità di una valutazione clinica
da parte dei professionisti della salute mentale per tutti i
candidati a un intervento di chirurgia estetica
"Variabili predittive di Objectifying Objectifying post-operatoria a seguito di interventi di chirurgia estetica".
No full textBody image and personality disorders in cosmetic surgery settings
No full textObjectives: Psychiatric disorders characterized by body image disorder (BID) such as body dysmorphic disorder, are relatively common in cosmetic surgery settings and several authors suggested the need for a preoperative clinical evaluation of Axis I and Axis II comorbidity. Study 1 investigated the prevalence of Personality Disorders (PDs) and Study 2 investigated the comorbidity between BID and PDs in patients seeking cosmetic surgery. Methods: Sixty two patients (study 1) scheduled for aesthetic rhinoplasty (62,9% F; Mage = 34.47 ± 10.69 ys) and 80 patients (study 2) scheduled for profile, breast and body contouring cosmetic surgery from two Italian hospitals (91% F; Mage = 32.68 ± 3.63) completed the Body Uneasiness Test (BUT) and the Personality Diagnostic Questionnaire - 4+ (PDQ-4+) with the exception of the items relating to two appendix PDs. Results: 19.6% and 17.5% of subjects (study 1 and 2, respectively), had at least 1 PD. In both studies, cluster B and C PDs are the most prevalent. In particular, the five most prevalent PDs were: obsessive-compulsive, avoidant, narcissistic, borderline and histrionic PD. In study 2, using the BUT cut-off score as a marker of clinical significance, 43.8% of subjects had a BID and all PD patients showed comorbidity with BID. Conclusion: Our study supports the evidence that PDs and BIDs are common in cosmetic surgery settings, as well as the importance of preoperative clinical evaluation of these disorders
Stevens-Johnson syndrome and toxic epidermal necrolysis: 11-year retrospective experience in a high-complexity tertiary hospital in Milan, Italy
No full textStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug-induced hypersensitivity reactions characterized by widespread epidermal necrosis, mucous membrane erosions, and systemic findings. We have provided our 11-year experience from a Milan, Italy tertiary hospital managing SJS/TEN, evaluating the clinical and histopathologic features plus the impact on mortality. We retrospectively analyzed 28 patients diagnosed with SJS/TEN based on the clinical and histopathologic findings, according to the classification criteria of multiple studies. We assessed the dermatographics, comorbidities, drug history, lesion characteristics, clinical findings, treatments, blood tests, and outcomes. Severity scores (SCORTEN, Re-SCORTEN, ABCD-10) were used for treatment evaluation and mortality prediction. Data were statistically analyzed, and significant factors associated with mortality were identified. We found that among the 28 patients, 89.2% had comorbidities, mainly cardiovascular diseases, and 21.4% had autoimmune disorders. All patients had received systemic therapy (46.6% monotherapy, 53.6% combination therapy), with systemic steroids (71.4%) and intravenous immunoglobulins (67.8%) being common treatments. There were complications, including systemic infections (67.9%) and septic shock (10.7%). The overall mortality rate was 17.8%. The statistical analysis indicated that malignancy, a high ABCD-10 score, and a high neutrophil-to-lymphocyte ratio were significantly associated with mortality. The extent of affected body surface area did not correlate significantly with mortality. This study provides insights into SJS/TEN management, revealing factors influencing mortality in a high-complexity tertiary hospital setting
Suspected breast implant rupture: our experience, recommendations on its management and a proposal for a model of informed consent
No full textMorphological analysis of JAK1 intracellular pathway activation after pro-inflammatory psoriatic cytokines exposure: inside-out and outside-in the epidermis
No full textFor their normal growth, cells depend on a continuous flow of signals from the environment. The Janus kinases (JAK) 1 transducers signalling pathway is a pleiotropic cascade used to transduce a multitude of signals among cells. A variety of ligands including cytokines, hormones, growth factors, and their receptors stimulate the JAK1 pathway. Cytokines, a large and very heterogeneous family of small and generally soluble glycoproteins, both control multiple biological processes as haematopoiesis, inflammation, and immunity playing a central role in cell-cell communication. Their action is mediated by the binding to specific receptors on the cell surface, thus transducing biological information to target cells [1]. Pro-inflammatory cytokines play a pivotal role in several inflammatory illnesses including psoriasis. Among them, interleukin (IL)-17, IL-22, IL-23 and tumor necrosis factor (TNF)-alpha play a central role. In the formation and progression of the psoriatic lesion a typical marker is keratin (K) 17 which is correlated with psoriasis severity. The aims of this study were to evaluate the early, direct, and specific effects of pro-inflammatory psoriatic cytokines i) on the activation of the intracellular pathway JAK1 and ii) on the correlation with the induction of K17 expression in a three-dimensional model (3D) of human skin (n=7) by immunofluorescence. Biopsies were cultured overnight epidermal side-up in a Transwell system and exposed to 50 ng/ml IL-17, or 100 ng/ml IL-22, or 50 ng/ml IL-23 or 100 ng/ml TNF-alpha. Samples were harvested 24 (T24), 48 (T48), and 72 (T72) hours after cytokine incubation.
In samples not exposed to cytokines, a JAK1 slight labelling was observed throughout the epidermis, decreasing at T72 in the lower layers. At T24, IL-17 and IL-22, but not IL-23 and TNF-alpha, induced an expression of JAK1 in the spinous layer. At T72, JAK1 immunostaining decreased in all samples, similarly to controls. K17 immunopositivity was induced and progressively increased with time in the suprabasal layers of epidermis in all experimental groups, with the exception of the TNF-alpha group. These results suggest that cytokines exert parallel effects on JAK1 pathway activation and K17 induction.
In conclusion, 3D this model, reproducing some features of psoriatic microenvironment, represents a useful experimental approach to dissect the specific role of each cytokine in the different steps of psoriatic lesion formation
Il lembo osteomuscolare di temporale nella riparazione dei gravi difetti della mandibola.
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