A miRNAs catalogue from third-stage larvae and extracellular vesicles of Anisakis pegreffii provides new clues for host-parasite interplay.

Anisakids are widespread marine parasites of medical, veterinary and economic relevance. They infect marine natural hosts but humans can accidentally acquire the fish-borne zoonosis anisakiasis by ingesting infected raw fishes or mollusks. Among the several species described, Anisakis pegreffii is one of the main etiological agent of the disease, in particular in the Mediterranean area. Despite the growing evidence of miRNAs involvement in host-parasite interplay, and the emerging role of exosomal microvesicles in shuttling them between different cell types (and sometime across species), no information on miRNAs from any Anisakis species is presently available. In this study we isolated extracellular vesicles (EVs) released by Anisakis pegreffii infective third-stage larvae (L3) and analyzed by RNA-seq small RNAs from both L3 and EVs. We showed by nanoparticle tracking analysis that L3 release in culture medium particles of size compatible with the one of extracellular vesicles. A catalogue of 156 miRNAs from A. pegreffii was compiled by sequence comparison to evolutionary close species and miRNA prediction software. Using differential expression analysis, we identified a small number of highly abundant miRNAs in larvae and extracellular vesicles fractions whose potential biological relevance may deserve future investigation. Finally, A. pegreffii miRNAs were compared to those described in other parasitic helminths and predicted targets among human genes were searched, suggesting their potential involvement during infection.

Switch from twice-daily tacrolimus (Prograf) to once-daily prolonged-release tacrolimus (Advagraf) in kidney transplantation.

Advagraf is a new modified-release once-daily formulation of tacrolimus. The aim of this study was to define the efficacy and safety of switching from Prograf to Advagraf immunosuppression in kidney transplant recipients. The switched dose ratio of Prograf to Advagraf was 1:1. Forty-one patients (34 men and 7 women) were switched at 36.6 ± 16.1 months after kidney transplantation. All patients maintained stable renal function and the conversion. In 16 subjects it was possible to withdraw steroid administration after obtaining adequate Advagraf blood levels, among whom 14 remained steroid free. Adverse events, including dizziness and tinnitus, were reported in 1 patient, who was reverted to Prograf. One patient who was receiving triple therapy with low tacrolimus blood levels experienced are acute rejection episode. The switch to Advagraf was safe and efficacious in kidney transplant recipients with or without steroid administration. Moreover, interruption of steroid was possible and well tolerated after achieving adequate stable blood levels with Advagraf.

Prospective study of switch from cyclosporine to tacrolimus for fibroadenomas of the breast in kidney transplantation.

INTRODUCTION: Breast fibroadenomas may result from exposure to cyclosporine (CsA). The aim of this prospective study was to assess the reversibility of breast fibroadenomas following conversion from CsA to tacrolimus among a small cohort of female renal transplant recipients. METHODS: Following renal transplantation, fibroadenomas either developed or progressed in eight Caucasian female patients with CsA-based immunosuppression. These patients were enrolled in a pilot study assessing whether conversion from a CsA-based to a tacrolimus-based regimen prevented progression of breast disease or reversed existing lumps. Patients underwent a baseline visit in which we assessed the clinical history, number and dimension of fibroadenomas, graft function and hormonal profile (FSH prolactin, estradiol and progesterone). Twenty-one lumps were described in six patients; in addition, two patients had "grapes of fibroadenomas," of nondefinable numbers. RESULTS: Patients underwent conversion to tacrolimus after a mean of 63.8 +/- 37.4 months after renal transplantation. Of the 21 clearly described lumps complete reversibility was observed for eight fibroadenomas. Other fibroadenomas either decreased in size or remained stable without further progression. These changes were reported within 1 year following conversion to tacrolimus. CONCLUSION: A switch from CsA to tacrolimus was effective to prevent the progression of fibroadenomas. In female renal transplant recipients with CsA-based immunosuppression suffering from breast fibroadenomas, early CsA withdrawal may avoid the need for breast surgery.

A rare case of cystic variety of angiomatoid fibrous histiocytoma.

A rare case of cystic angiomatoid fibrous histiocytoma of the thigh in a 13-years-old girl is reported. Final diagnosis was made only after surgical excision. A review of the literature with a discussion of the particularity of this case are also examined in order to achieve the best surgical strategy and the lower risk of recurrence.

Genetic polymorphisms associated with outcome in multiple myeloma patients receiving high-dose melphalan.

High-dose melphalan (HDM) is an essential component in the treatment of patients with multiple myeloma (MM). Few data are available regarding genetic polymorphisms associated with patient outcome or toxicity in this setting. To identify such polymorphisms, we performed a retrospective analysis, genotyping single nucleotide polymorphisms (SNPs) with the arrayed primer extension (APEX) technology in 169 patients having received HDM for MM. We analyzed 209 SNPs in 95 genes involved in drug metabolism, DNA repair, cell cycle and apoptosis. SNPs in ABCB1, CYP3A4 and TP53BP2 were associated with response to VAD induction therapy (P<0.01). SNPs in ALDH2, GSTT2 and BRCA1 were associated with response to HDM (P<0.01). Polymorphisms in CYP1A1, RAD51 and PARP were associated with disease progression whereas polymorphisms in ALDH2 and CYP1A1 were correlated with OS. Polymorphisms in BRCA1, CDKN1A and XRCC1 were associated with the occurrence of severe mucositis after HDM. These results suggest that SNPs of genes involved in drug metabolism or DNA repair could be used to distinguish MM patient subgroups with different toxicity/efficacy profiles.