Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells from Patients with Crohn's Disease.

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) which is the precursor of the photosensitizer protoporphyrin IX (PpIX) is an available treatment for several diseases. ALA-PDT induces the apoptosis and necrosis of target lesions. We have recently reported the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). This study has investigated the ALA-PDT-mediated effects on PBMC subsets from patients with active Crohn's disease (CD). No effects on lymphocyte survival after ALA-PDT were observed, although the survival of CD3-/CD19+ B-cells seemed slightly reduced in some samples. Interestingly, ALA-PDT clearly killed monocytes. The subcellular levels of cytokines and exosomes associated with inflammation were widely downregulated, which is consistent with our previous findings in PBMCs from healthy human subjects. These results suggest that ALA-PDT may be a potential treatment candidate for CD and other immune-mediated diseases.

Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment. We report from the first study on the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). The treatment reduced the cytokines and exosomes studied, although there was variation among individual PBMC samples. This reduction is consistent with PDT-mediated survivals of subsets of PBMCs. More specifically, the ALA-PDT treatment apparently decreased all pro-inflammatory cytokines included, suggesting that this treatment may provide a strong anti-inflammatory effect. In addition, the treatment has decreased the levels of different types of exosomes, the HLA-DRDPDQ exosome in particular, which plays an important role in the rejection of organ transplantation as well as autoimmune diseases. These results may suggest future therapeutic strategies of ALA-PDT.

[Declining prevalence of proliferative retinopathy in patients with type 1 diabetes]. / Redusert forekomst av proliferativ retinopati ved type 1-diabetes?

BACKGROUND: It is likely that improved treatment of diabetes during the last decades has led to a declining prevalence of retinopathy. We have assessed whether this is the case for patients with type I diabetes. MATERIAL AND METHODS: Medical records were retrospectively reviewed for all patients who were diagnosed with type 1 diabetes in the periods 1960-1975 (early group) and 1985-1990 (late group) at the diabetes clinic in St. Olavs Hospital (Trondheim). Information on the prevalence of retinopathy ten and 15 years after diabetes onset was obtained from hospital records and private ophthalmologists in Trondheim. RESULTS: 125 patients were identified in the early group and 147 patients in the late group. The prevalence of proliferative retinopathy was higher in the early group than in the late group, both after ten years (4% vs. 0%, p = 0.04) and 15 years (13% vs. 5%, p = 0.04) of diabetes. The prevalence of background retinopathy was not significantly different between the two groups after ten (12% vs. 14%, p = 0.70) or 15 years (29% vs. 24%, p = 0.36) of diabetes. INTERPRETATION: Our results indicate that the prevalence of proliferative retinopathy is decreasing in patients with type 1 diabetes in Norway. Explanations may be improved follow-up and treatment of diabetes and diabetic retinopathy.