The history of Lyme disease in Italy and its spread in the Italian territory.

Lyme borreliosis (LB) is the most common vector-borne zoonotic inflammatory disease in the Northern Hemisphere. In Italy, the first case was diagnosed in 1985 in a woman in Liguria, while the second, in 1986 in Friuli-Venezia Giulia, documenting the infection in northern Italy. Both diagnoses were confirmed by serological assessment by an indirect immunofluorescence (IFI) technique. Borrelia cultivation from both Ixodes ricinus ticks and human lesions in Trieste (Friuli-Venezia Giulia) identified Borrelia afzelii as the prevalent genospecies; nevertheless, Borrelia garinii, Borrelia burgdorferi (sensu stricto), and Borrelia valaisiana (VS116 Group) were also detected, although less frequently. LB was also documented in other Italian regions: in Tuscany (1991), Trentino-Alto Adige (1995-1996), Emilia-Romagna (1998), Abruzzo (1998), and more recently, Lombardy. Nevertheless, data on LB in other Italian regions, especially in southern Italy and islands, are poor. The aim of this study is to document the spread of LB in Italy through the collection of data from LB patients in eight Italian hospitals located in different Italian regions. Diagnostic criteria for LB diagnosis are as follows: i) the presence of erythema migrans (EM) or ii) a clinical picture suggestive of LB, confirmed by serological tests and/or PCR positivity for Borrelia detection. In addition, data also included the place of residence (town and region) and the place where patients became infected. During the observation period, 1,260 cases were gathered from the participating centers. Although different in extent from northern Italy to central/southern Italy, this study shows that LB is widespread throughout Italy.

A novel telomerase activity and microRNA-21 upregulation identified in a family with palmoplantar keratoderma.

Palmoplantar keratoderma is a set of skin diseases with hyperkeratotic thickening of palms and soles which are characteristic of these heterogeneous group of keratinization disorders. Various genetic mutations, autosomal dominant or recessive, have been identified which may triggerpalmoplantar keratoderma, as KRT9 (Keratin 9), KRT1 (Keratin1), AQP5 (Aquaporin), SERPINB 7 (serine protease inhibitor). The identification of causal mutations is extremely important for the correct diagnosis. Here, we report the case of a family affected from Palmoplantar keratoderma caused by autosomal dominant KRT1 mutations (Unna-Thost disease). Telomerase activation and hTERT expression take a part in the process of cell proliferation and inflammation and microRNAs, as microRNA-21, are emerging as drivers in the regulation of telomerase activity. Here, the patients underwent KRT1 analysis genetic sequence, telomerase activity and miR-21 expression. Beside histopathology assay was performed. The patients presented thickening of the skin on soles of the feet and the palms of the hands, KRT1mutations and showed high expression levels of hTERT and hTR, the gene encoding for the telomeric subunits, and miR-21 (fold change > 1.5 and p value = 0.043), explicating the aberrant proliferation of epidermal layer and the inflammatory state characterizing palmoplantar keratoderma.

miR-34 modulates apoptotic gene expression in Ingenol mebutate treated keloid fibroblasts.

Keloids are benign skin tumors that develop in individuals who have a positive family history of keloid disorders. Keloids are characterized by a deregulated wound­healing process, atypical fibroblasts with extreme deposition of extracellular matrix components, particularly collagen, increased cell proliferation and associated failure of apoptosis. Recently ingenol­mebutate has been used as a novel agent with anti­proliferative activity on human keloids as an alternative treatment option in patients, once conventional therapies have failed. We hypothesized that microRNAs (miR/miRNA) may be involved in the balance between lesion formation and repair. A comprehensive understanding of the molecular mechanism underlying the Ingenol­mebutate response in keloid fibroblast following Ingenol­mebutate exposure has been established previously. Therefore, the present study analyzed changes in miRNAs and apoptotic gene regulation in Ingenol­mebutate treated keloid fibroblast, by reverse transcription­quantitative polymerase chain reaction and a DNA fragmentation assay. The range of upregulated miRNAs and downregulated genes encoding cell death appeared to be associated with the degree of the morphological alterations in Ingenol­mebutate treated keloids. In particular, the upregulation of miR­34a was detected in keloid fibroblasts during and following Ingenol­mebutate exposure. Keloid fibroblasts that overexpressed miR­34a showed differential expression of genes involved in the apoptotic signaling pathway such as p53. In conclusion, the Ingenol­mebutate treatment used here was effective in reducing keloid fibroblast growth in cell culture experiments and the expression of particular miRNAs modulated the pro­apoptotic gene expression following Ingenol-mebutate treatment.

Ingenol mebutate treatment in keloids.

BACKGROUND: Ingenol-mebutate has been used for the treatment of actinic keratosis. It has been shown that ingenol-mebutate inhibits the growth of cancer cells or induces tumor cell death through pro-apoptotic effects. Keloids are benign skin tumours and are the effect of a deregulated wound-healing process in genetically predisposed patients. Increased cell proliferation, which accounts for the progressive and hypertrophic nature of keloids, correlates with the failure of apoptosis and plays a role in the process of pathological scarring. Keloid cells show a mutated p53 gene resulting in functionally inactive p53 protein which cannot control genomic integrity. They tend to escape from apoptosis which leads to keloid development by means of accumulation of continuously proliferating cells. Currently, the treatment of keloids remains a challenge for high recurrence rates. However, the design and the development of pro-apoptotic therapeutic strategies would be beneficial to keloids treatment. CASE PRESENTATION: A 55-year-old caucasian woman presented recurrent keloids on a presternal scar. Standard surgical intervention was used to treat the scar. However, this was unsuccessful and a year later the patient sought treatment again, but only by alternative means as the patient refused further surgical intervention. Consequently, based on past research and experience, the authors attempted to treat these lesions with ingenol mebutate gel, due to the pro-apoptotic effects. CONCLUSION: After 1 month, there was a clinical resolution of lesions, with a slightly squamous, post-inflammatory erythema. A cutaneous biopsy proved the absence of residual keloids and deregulated expression of molecular markers. The last follow-up of the patient, 1 year after treatment, showed that the patient was still free of keloids recurrence.

Effect of selenocystine on gene expression profiles in human keloid fibroblasts.

In this study, selenocystine, a nutritionally available selenoamino acid, was identified for the first time as a novel agent with anti proliferative activity on human keloids. The 20 µM concentration after 48 h treatment used here was the most effective to reduce keloid fibroblast growth. We analyzed the gene expression profile of selenocystine treatment response in keloid fibroblasts by the microarray system to characterize the effects of selenocystine on human keloids. The major alterations in keloid fibroblasts following selenocystine exposure included up-regulation of the genes encoding cell death and transcription factors. Prominent down-regulation of genes involved in development, cell adhesion and cytoskeleton, as well as extra cellular matrix genes, usually strongly up-regulated in keloids, resulted following selenocystine exposure. The range of the down-regulated genes and the degree of the decreased expression appeared to be correlated with the degree of the morphological alterations in selenocystine treated keloids.

Telomere shortening may be associated with human keloids.

BACKGROUND: Keloids are benign skin tumors that are the effect of a dysregulated wound-healing process in genetically predisposed patients. They are inherited with an autosomal dominant mode with incomplete clinical penetrance and variable expression. Keloids are characterized by formation of excess scar tissue beyond the boundaries of the wound. The exact etiology is still unknown and there is currently no appropriate treatment for keloid disease. METHODS: We analyzed sample tissues were obtained from 20 patients with keloid skin lesions and normal skin was obtained from 20 healthy donors. The telomeres were measured by Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay. Quantitative Real-Time RT-PCR analysis of hTERT gene expression was performed and intracellular ROS generation was measured. RESULTS: In this study, we determined whether telomeric shortening and the expression of human telomerase reverse transcriptase (hTERT) occurs in keloid patients. Using Terminal Restriction Fragment (TRF) analysis and Real-Time PCR assay, we detected a significant telomere shortening of 30% in keloid specimens compared to normal skin. Using quantitative Real-Time RT-PCR, telomerase activity was found absent in the keloid tissues. Moreover, an increase in ROS generation was detected in fibroblasts cell cultures from keloid specimens as more time elapsed compared to fibroblasts from normal skin. CONCLUSION: Telomere shortening has been reported in several metabolic and cardiovascular diseases. We found that telomere shortening can also be associated with human keloids. Chronic oxidative stress plays a major role in the pathophysiology of several chronic inflammatory diseases. Here we found increased ROS generation in fibroblasts from keloid fibroblasts cell cultures when compared to normal skin fibroblasts. Hence we conclude that oxidative stress might be an important modulator of telomere loss in keloid because of the absence of active telomerase that counteracts telomere shortening.