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Nephrotic syndrome rarely occurs in the first year of life. There are some cases which share the pathological changes observed in older children or in adults, but two forms, the congenital nephrotic syndrome of the Finnish type (CNF) and the diffuse mesangial sclerosis (DMS) show peculiar morphologic findings. CNF is characterized in its early phases by the focal dilation of the proximal tubules with formation of small cysts and by mesangial hypercellularity. With progression of the disease, tubular dilation spreads from the deep to the outer cortex and focal-segmental and global glomerulosclerosis become evident. DMS may be renal-limited or be associated with male pseudohermaphroditism and Wilm’s tumor (Denys-Drash syndrome). It shows the increase of the mesangial matrix and mesangial hypercellularity in the early phases of the disease and extensive glomerulosclerosis in the later ones. Podocytes are hypertrophic around the sclerotic areas and form pseudocrescents. Tubular dilations and cysts may be present, but in lesser extent compared with CNF. Interstitial fibrosis occurs with increasing severity from the inner to the outer cortex. Apart from the negative reaction from nephrin in CNF, immunohistochemistry has no diagnostic relevance in both diseases. Electron microscopy shows in both diseases a diffuse effacement of the foot processes and microvillous transformation of the podocytes. Glomerular basement membrane may show changes recalling those found in Alport disease. Due to the rather similar changes in CNF and DMS, a pathological diagnosis may be difficult on small tissue specimens provided by needle biopsies. It follows that accurate clinical and genetic investigations are needed in addition to the pathological study. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014) · Cagliari (Italy) · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

BACKGROUND: Like other steroid hormones, vitamin D elicits both transcriptional events and rapid non genomic effects. Vitamin D receptor (VDR) localization and mechanisms of VDR-triggered non genomic responses are still controversial. Although anticoagulant effects of vitamin D have been reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids. METHODOLOGY/PRINCIPAL FINDINGS: In this study we characterized the expression and cellular localization of VDR in human platelets and in a megakaryocyte lineage. Human platelets and their TPA-differentiated precursors expressed a classical 50 kDa VDR protein, which increased with megakaryocytes maturation. By biochemical fractionation studies we demonstrated the presence of the receptor in the soluble and mitochondrial compartment of human platelets, and the observation was confirmed by immunoelectron microscopy analysis. Similar localization was found in mature megakaryocytes, where besides its classical nuclear localization the receptor was evident as soluble and mitochondria resident protein. CONCLUSIONS: The results reported here suggest that megakaryocytopoiesis and platelet activation, which are calcium-dependent events, might be modulated by a mitochondrial non genomic activity of VDR. These data open challenging future studies on VDR physiological role in platelets and more generally in mitochondria.

Background. Type II mixed cryoglobulinaemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, and sustained by proliferation of oligoclonal cells. Systemic B-cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (Rituximab). Similar effects could be expected in type II MC.Methods. Six patients, mean age 64.2 years (range: 3776 years), with HCV infection genotype 2a2c (three cases) or 1b (three cases) and symptomatic type-II MC with systemic manifestations, including renal involvement (five cases) and bone marrow clonal restriction (three cases), were considered eligible for Rituximab therapy. Rituximab was administered intravenously at a dose of 375?mg/m2 on days 1, 8, 15 and 22. Two more doses were administered 1 and 2 months later. No other immunosuppressive drugs were added. Response was evaluated by assessing the changes in clinical signs, symptoms and laboratory parameters for =18 months.Results. Levels of proteinuria, erythrocyte sedimentation rate and cryocrit significantly decreased at 2, 6 and 12 months. Rheumatoid factor and IgM significantly decreased at 6 months whereas C4 values significantly increased at 2 and 6 months. HCV viral load and immunoglobulin G remained stable. Bone marrow abnormalities were found to reverse to normal in all three positive cases. Constitutional symptoms (skin ulcers, purpura, arthralgia, weakness, paraesthesia and fever) disappeared or improved. No acute or delayed side effects were observed.Conclusions. Rituximab appears to be a safe and effective therapeutic option in symptomatic patients with HCV-associated MC glomerulonephritis and signs of systemic vasculitis. [ABSTRACT FROM AUTHOR]